Numerous studies shown that structural hippocampal alterations are present in subjects at high risk of developing psychosis or schizophrenia. These findings indicate that in a subset of patients undergoing first-psychosis episode (FPE), hippocampal volume alterations are accompanied by associated cognitive and neuropsychological deficits. The combination of psychological deficits and neuroanatomical alterations, in turn, appears to increase treatment complexity and worsen clinical outcomes.

We aim to determine whether cognitive and neuropsychological functioning deficits precede or follow hippocampal alterations during early onset psychosis.

This cross-sectional study describes 3 case-studies of adolescent subjects, ages 16–17, admitted at the child and adolescent inpatient psychiatric unit in lieu of first psychotic episode. We conducted detailed structured clinical psychiatric interviews, anatomical-structural magnetic resonance imaging (MRI), sleep-deprived electroencephalogram (EEG) recordings, laboratory testing, and a comprehensive battery of psychological testing to better understand their clinical pictures.

Psychological testing in each patient demonstrated the presence of low to borderline intellectual functioning coupled with neuropsychological deficits in different psychiatric domains. Interestingly, these changes coincided with structural MRI alterations in the hippocampal area.

Our case report adds to the armamentarium of literature signifying that radiologically detectable alterations of the hippocampus may occur either concomitantly or closely following the development of early cognitive deficits in patients with FPE.

Our aim was to summarize the efficacy and safety of atomoxetine, amphetamines, and methylphenidate in schizophrenia.

We undertook a systematic review, searching PubMed/Scopus/Clinicaltrials.gov for double-blind, randomized, placebo-controlled studies of psychostimulants or atomoxetine in schizophrenia published up to 1 January 2017. A meta-analysis of outcomes reported in two or more studies is presented.

We included 22 studies investigating therapeutic effects of stimulants (k=14) or measuring symptomatic worsening/relapse prediction after stimulant challenge (k=6). Six studies of these two groups plus one additional study investigated biological effects of psychostimulants or atomoxetine. No effect resulted from interventional studies on weight loss (k=1), smoking cessation (k=1), and positive symptoms (k=12), and no improvement was reported with atomoxetine (k=3) for negative symptoms, with equivocal findings for negative (k=6) and mood symptoms (k=2) with amphetamines. Attention, processing speed, working memory, problem solving, and executive functions, among others, showed from no to some improvement with atomoxetine (k=3) or amphetamines (k=6). Meta-analysis did not confirm any effect of stimulants in any symptom domain, including negative symptoms, apart from atomoxetine improving problem solving (k=2, standardized mean difference (SMD)=0.73, 95% CI=0.10–1.36, p=0.02, I2=0%), and trending toward significant improvement in executive functions with amphetamines (k=2, SMD=0.80, 95% CI=−1.68 to +0.08, p=0.08, I2=66%). In challenge studies, amphetamines (k=1) did not worsen symptoms, and methylphenidate (k=5) consistently worsened or predicted relapse. Biological effects of atomoxetine (k=1) and amphetamines (k=1) were cortical activation, without change in β-endorphin (k=1), improved response to antipsychotics after amphetamine challenge (k=2), and an increase of growth hormone–mediated psychosis with methylphenidate (k=2). No major side effects were reported (k=6).

No efficacy for stimulants or atomoxetine on negative symptoms is proven. Atomoxetine or amphetamines may improve cognitive symptoms, while methylphenidate should be avoided in patients with schizophrenia. Insufficient evidence is available to draw firm conclusions.

Two similarly designed extension studies evaluated the long-term safety and tolerability of desvenlafaxine for the treatment of children and adolescents with major depressive disorder (MDD). Efficacy was evaluated as a secondary objective.

Both 6-month, open-label, flexible-dose extension studies enrolled children and adolescents who had completed one of two double-blind, placebo-controlled, lead-in studies. One lead-in study included a 1-week transition period prior to the extension study. Patients received 26-week treatment with flexible-dose desvenlafaxine (20–50 mg/d). Safety assessments included comprehensive psychiatric evaluations, vital sign assessments, laboratory evaluations, 12-lead electrocardiogram, physical examination with Tanner assessment, and Columbia-Suicide Severity Rating Scale. Adverse events (AEs) were collected throughout the studies. Efficacy was assessed using the Children’s Depression Rating Scale–Revised (CDRS-R).

A total of 552 patients enrolled (completion rates: 66.4 and 69.1%). AEs were reported by 79.4 and 79.1% of patients in the two studies; 8.9 and 5.2% discontinued due to AEs. Treatment-emergent suicidal ideation or behavior was reported for 16.6 and 14.1% of patients in the two studies. Mean (SD) CDRS-R total score decreased from 33.83 (11.93) and 30.92 (10.20) at the extension study baseline to 24.31 (7.48) and 24.92 (8.45), respectively, at week 26.

Desvenlafaxine 20 to 50 mg/d was generally safe and well tolerated with no new safety signals identified in children and adolescents with MDD who received up to 6 months of treatment in these studies. Patients maintained the reduction in severity of depressive symptoms observed in all treatment groups at the end of the lead-in study.

To compare the tolerability and efficacy of different antipsychotic cross-titration schedules, using data from a brexpiprazole study (Equator; NCT01668797).

Patients with schizophrenia were cross-titrated from other antipsychotics to brexpiprazole monotherapy in a 1–4 week open-label conversion phase, then entered a single-blind brexpiprazole treatment phase. Patients were stratified into four “conversion groups,” according to the amount of time spent in the conversion phase. Discontinuation rates, treatment-emergent adverse events (TEAEs), and efficacy (Positive and Negative Syndrome Scale [PANSS]) were compared between conversion groups.

Of the 404 patients treated with brexpiprazole, the majority (72.0%) spent 22–33 days in the conversion phase. Discontinuation rates due to lack of efficacy or adverse events were low in all conversion groups. Of the 292 patients who successfully switched and completed 8 weeks of brexpiprazole treatment, most were converted to brexpiprazole over 22–33 days (80.1%), and fewer were converted over 1–7 days (2.4%), 8–14 days (6.5%), or 15–21 days (11.0%). The incidence of TEAEs over 8 weeks was lower among those converted over 22–33 days (44.4%) than in other conversion groups (62.5–84.2%), although low patient numbers with shorter conversion times limit the generalizability of this finding. Each conversion group showed comparable improvement in PANSS total score from baseline.

The majority of patients were cross-titrated to brexpiprazole over a period of 22–33 days, by investigators’ choice. Additional data on shorter conversions may help clinicians to choose a switching paradigm that best meets their patients’ needs.

It is crucial to clarify the structure of attention-deficit/hyperactivity disorder (ADHD) symptomatology in all age groups to determine how to best conceptualize this disorder across the lifespan. We tested the ADHD factor structure across adulthood and investigated independent associations with executive functions.

Data from 645 adults aged 18–59 and 233 adults aged 60–85 were drawn from the Nathan Kline Institute Rockland Sample. Participants completed the Conners Adult ADHD Rating Scale and tests of executive functioning. Invariance of the ADHD factor structure was investigated using confirmatory factor analyses. Associations with cognition were explored using multiple linear regression.

Results confirmed a bifactor model with 3 specific factors (inattention, hyperactivity, and impulsivity). Factor loadings and item intercepts were invariant across ages. Levels of hyperactivity and impulsivity were lower in older adults. Inattentive symptoms in young adults were positively related to cognitive flexibility. In older adults, ADHD symptoms predicted poorer working memory.

ADHD symptoms manifest similarly across adulthood. The lack of robust associations between ADHD symptomatology and executive functions raises concerns about the usefulness of neuropsychological measures in diagnosing adult ADHD. These results support the validity of the ADHD concept in older adults but suggest a need for age-appropriate normative criteria.

In this study, we compared duration of untreated illness (DUI) in obsessive-compulsive disorder (OCD), panic disorder (PD), and social anxiety disorder (SAD) patients and investigated its correlates, both within specific diagnoses and across the whole sample.

Eighty-eight patients (33 OCD, 24 SAD, and 31 PD) had their diagnosis confirmed by the Mini International Neuropsychiatric Interview, were assessed for treatment-seeking variables, and were evaluated with instruments aimed at quantifying transdiagnostic features (i.e., the Cause subscale of the Illness Perception Questionnaire–Mental Health and the Anxiety Sensitivity Index–Revised) and severity of illness (i.e., Beck Depression and Anxiety Inventories, the Dimensional Obsessive-Compulsive Scale, the Panic and Agoraphobia Scale, and the Social Phobia Inventory).

The only differences between groups with short (<2 years) versus long (>2 years) DUI were greater fear of public display of anxiety in the first group and greater social avoidance in the second group. The DUI was significantly different between groups that sought treatment after the onset of illness, with OCD patients having longer DUI than PD patients and shorter DUI than SAD patients. Further, DUI correlated negatively with the perception of OCD being caused by stress and positively with severity of panic-related disability in SAD patients, but not in PD or OCD patients.

There was substantial delay in treatment seeking among the anxiety and obsessive-compulsive disorder patients, particularly those with OCD or SAD. Perception of stress as a cause of OCD prompted treatment seeking, while severity of panic symptoms delayed treatment seeking.

An obsessive-compulsive disorder (OCD) subtype has been associated with streptococcal infections and is called pediatric autoimmune neuropsychiatric disorders associated with streptococci (PANDAS). The neuroanatomical characterization of subjects with this disorder is crucial for the better understanding of its pathophysiology; also, evaluation of these features as classifiers between patients and controls is relevant to determine potential biomarkers and useful in clinical diagnosis. This was the first multivariate pattern analysis (MVPA) study on an early-onset OCD subtype.

Fourteen pediatric patients with PANDAS were paired with 14 healthy subjects and were scanned to obtain structural magnetic resonance images (MRI). We identified neuroanatomical differences between subjects with PANDAS and healthy controls using voxel-based morphometry, diffusion tensor imaging (DTI), and surface analysis. We investigated the usefulness of these neuroanatomical differences to classify patients with PANDAS using MVPA.

The pattern for the gray and white matter was significantly different between subjects with PANDAS and controls. Alterations emerged in the cortex, subcortex, and cerebellum. There were no significant group differences in DTI measures (fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity) or cortical features (thickness, sulci, volume, curvature, and gyrification). The overall accuracy of 75% was achieved using the gray matter features to classify patients with PANDAS and healthy controls.

The results of this integrative study allow a better understanding of the neural substrates in this OCD subtype, suggesting that the anatomical gray matter characteristics could have an immune origin that might be helpful in patient classification.

Internet gaming disorder (IGD) is becoming a matter of concern around the world. However, the neural mechanism underlying IGD remains unclear. The purpose of this paper is to explore the differences between the neuronal network of IGD participants and that of recreational Internet game users (RGU).

Imaging and behavioral data were collected from 18 IGD participants and 20 RGU under a probability discounting task. The independent component analysis (ICA) and graph theoretical analysis (GTA) were used to analyze the data.

Behavioral results showed the IGD participants, compared to RGU, prefer risky options to the fixed ones and spent less time in making risky decisions. In imaging results, the ICA analysis revealed that the IGD participants showed stronger functional connectivity (FC) in reward circuits and executive control network, as well as lower FC in anterior salience network (ASN) than RGU; for the GTA results, the IGD participants showed impaired FC in reward circuits and ASN when compared with RGU.

These results suggest that IGD participants were more sensitive to rewards, and they were more impulsive in decision-making as they could not control their impulsivity effectively. This might explain why IGD participants cannot stop their gaming behaviors even when facing severe negative consequences.

Because ethically and practically a randomized control trial of antipsychotics will never be done, we recently conducted and reported a 8- to 50-year, naturalistic follow-up from an academic clinic of patients with chronic schizophrenia on antipsychotic medication. We found that better medication adherence was a statistically significant predictor of better long-term global outcome and life satisfaction. Because there were important limitations on our findings, we now in this communication, using similar methodology, detail outcomes for a very different sample—inner city patients with chronic schizophrenia with a long past history of antipsychotic treatment, who were enrolled in clinical trials for new medications for schizophrenia.

This is a retrospective, naturalistic, longitudinal 6- to 49-years antipsychotic treatment (mean average, 20) follow-up of a consecutive series of patients volunteering for screening for studies with schizophrenia. Lifetime data were collected on (1) their medication adherence, (2) long-term global outcome, and (3) life satisfaction. Outcomes were rated by 2 different clinicians, 1 with information on medication adherence (nonblind rater) and 1 without (blind rater). We used linear regression models adjusted for age, family support, substance use disorder, race, marital status, and number of years in treatment to estimate the association between adherence and each outcome.

A total of 34 patients were assessed. Medication adherence was positively associated with the blind clinician’s rating of global outcome (P value=0.03) and the global assessment of functioning (P value=0.05). In the nonblinded clinician rating, medication adherence was unrelated to global outcome (P value=0.26) and to patients’ report of life satisfaction (P value=0.54).

This replication study, like our previous study, is not inconsistent with the recommendation for continuous, long-term treatment for chronic schizophrenia unless medically contraindicated.

Psychiatric disorders are often considered the leading cause of violence. This may be due to a stereotype created by media and general opinion.

The Modified Overt Aggression Scale (MOAS) was used to evaluate the severity of aggressive and violent behaviors in 400 patients who attended a post-acute psychiatric service in Milan from 2014 to 2016 and suffered from different psychiatric disorders. The psychopathological clinical picture was evaluated by Clinical Global Impression (CGI). The study also assessed the possible correlation between epidemiologic and sociodemographic factors, clinical variables, and aggression and violence.

Of the total number of subjects, 21.50% showed a MOAS score >0, 11.50% presented mild aggression (0–10 MOAS weighted score), 9% moderate aggression (11–20), and 1% severe aggression (MOAS >20). With respect to violent behaviors, 16% of patients showed a score >0 in one MOAS subscale other than verbal aggression according to violence definition. The severity of clinical picture seemed to be related to higher weighted MOAS score. Multivariate testing of different sociodemographic and clinical variables showed that violence was related to unemployment status, and significantly correlated to compulsory admission (TSO), suicide attempts (TS), and personality disorders, while the severity of clinical psychiatric picture seemed to play a secondary role.

Results have shown that personality disorders and sociodemographic factors, including economic factors, seem to be major determinants of violence among patients diagnosed with mental disorders.