Negative symptoms in schizophrenia are heterogeneous and multidimensional; effective treatments are lacking. Cariprazine, a dopamine D3-preferring D3/D2 receptor partial agonist and serotonin 5-HT1A receptor partial agonist, was significantly more effective than risperidone in treating negative symptoms in a prospectively designed trial in patients with schizophrenia and persistent, predominant negative symptoms.

Using post hoc analyses, we evaluated change from baseline at week 26 in individual items of the Positive and Negative Syndrome Scale (PANSS) and PANSS-derived factor models using a mixed-effects model for repeated measures (MMRM) in the intent-to-treat (ITT) population (cariprazine = 227; risperidone = 227).

Change from baseline was significantly different in favor of cariprazine versus risperidone on PANSS items N1-N5 (blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking) (P <.05), but not on N6 (lack of spontaneity/flow of conversation) or N7 (stereotyped thinking). On all PANSS-derived negative symptom factor models evaluated (PANSS-Factor Score for Negative Symptoms, Liemburg factors, Khan factors, Pentagonal Structure Model Negative Symptom factor), statistically significant improvement was demonstrated for cariprazine versus risperidone (P <.01). Small and similar changes in positive/depressive/EPS symptoms suggested that negative symptom improvement was not pseudospecific. Change from baseline was significantly different for cariprazine versus risperidone on PANSS-based factors evaluating other relevant symptom domains (disorganized thoughts, prosocial function, cognition; P <.05).

Since items representing different negative symptom dimensions may represent different fundamental pathophysiological mechanisms, significant improvement versus risperidone on most PANSS Negative Subscale items and across all PANSS-derived factors suggests broad-spectrum efficacy for cariprazine in treating negative symptoms of schizophrenia.

Adverse childhood experiences (ACE) exhibit long-lasting consequences on later life and are considered as a major public health problem. ACEs can be divided into household dysfunctions, which affect the child indirectly, and direct maltreatment. As a high correlation between ACEs in general is known, we assessed the risk for child maltreatment associated with the occurrence of household dysfunctions. To provide a better understanding for the mechanisms leading to the deleterious sequelae of ACEs, we furthermore assessed whether the long-term consequences of household dysfunction are mediated by child maltreatment and thereby might be targeted by effective child protection programs.

A representative sample of the German population above the age of 14 (N = 2531) was assessed in a cross-sectional observational population-based survey.

The data reveal that mental illness of a household member was associated with significantly increased risks for all child maltreatment subtypes (ORs 4.95–5.55), just as household substance abuse (ORs 5.32–6.98), violence against the mother (ORs 4.43–10.26), incarceration of a household member (ORs 6.11–14.93) and parental separation (OR 3.37–4.87). Child maltreatment partially mediated the association of household mental illness, substance abuse and parental separation with later depression, anxiety, life satisfaction and subjective general health status and completely mediated the associations of intimate partner violence (IPV) and incarceration of a household member with anxiety, depression and subjective health status in adulthood.

ACEs linked to household dysfunction are associated with an increased risk for all subtypes of child maltreatment. The assessed widespread consequences of household dysfunction are mediated by child maltreatment. This underlines the role of prevention of child maltreatment in families with household dysfunction and implies child protection as a priority in any interventions.

The duration of untreated illness (DUI) is a potentially modifiable parameter associated with worst prognosis in several psychiatric disorders, but poorly investigated in Obsessive-Compulsive Disorder (OCD). Our aims were to estimate the mean DUI in a large sample of individuals with OCD and its impact on response to the first ever adequate SRI treatment.

We retrospectively examined records of 251 patients with OCD (SCID-I, DSM-IV) who referred to our Department and were prospectively and naturalistically treated according to International Guidelines. The DUI was defined as the interval between age at onset and age at which patients received their first adequate pharmacological treatment. Response rates were compared in subjects with brief (≤24 months) versus long DUI. Logistic regression models predicting response and 12-week Y-BOCS score were run with DUI (among others) as independent variable.

The mean DUI was 106.19 ± 118.14 months, with a mean interval between onset of the disorder and when patients sought professional help of 82.27 ± 112.30 months. Response rates were significantly reduced in subjects with a long DUI, using both the cut-off of 24 months and the median value of 60 months. Regression analyses confirmed that a long (>24 months) DUI predicts poorer response and higher Y-BOCS scores at 12 weeks.

Our results, although preliminary, seem to suggest that a longer duration of untreated illness in OCD is associated with poorer outcome in terms of response to SRI treatments. It is imperative to do all the possible to shorten the DUI, both by improving access to mental health services, improving the ability of primary care physicians and mental health professionals to recognize OCD, and disseminate best-practice prescription guidelines.

Cognitive representations of an illness have an important impact on psychological outcomes. The current systematic review explored 1) the characteristics of illness representations held by parents of children and adults with serious mental illness (SMI), and 2) the associations of these representations with both parents’ and patients’ psychological outcomes.

PSYINFO and PUBMED were screened for eligible studies published between January 2000 and August 2018. Selection was based on PRISMA guidelines. Reference lists of these papers were checked for additional references. Two independent coders extracted all relevant data.

The search resulted in 31 relevant studies, which were divided, by type of methodology, into three sections: quantitative, qualitative, and mixed quantitative-qualitative. In each section, findings were divided in accordance with the two research questions.

Parents struggle to make meaning of their child’s illness, often holding stigmatizing ideas about the illness and blaming themselves for its existence. More longitudinal studies that include both of the child’s parents, as well as interventional studies, are needed to expand our knowledge of ways to help parents construct more beneficial representations of their children’s illnesses.

ADHD is a highly prevalent disease in childhood which often persists into adulthood, then co-occurring with common adult conditions. Especially for adult ADHD, little is known about the costs of ADHD and the additional costs of comorbid conditions.

To determine medical costs of ADHD and costs of comorbidities (mood, anxiety and substance use disorders, obesity), including their co-occurrence rates, stratified by age and gender.

Claims data from a German Statutory Health Insurance database with approximately four million member-records per year were analysed. A total of 25,300 prevalent ADHD patients were identified by means of an ICD-10 GM diagnosis of ADHD. A 1:1 age and gender adjusted reference group without ADHD diagnosis was randomly selected. Total health claims and health care costs related to ADHD were analysed, in addition to more targeted analyses of the occurrence and costs of pre-defined common comorbidities of, in particular, adult ADHD (SUD, mood and anxiety disorders, obesity). Outcomes were mean costs per patient and occurrence rates of comorbid conditions. Surplus costs of a comorbid condition in persons with ADHD relative to costs of this condition in persons without ADHD were calculated. Subgroup analyses were conducted based on age (0–12 years, 13–17 years, 18–30years, 30+ years) and gender.

Patients with ADHD were €1500 more expensive annually than individuals without ADHD (p < 0.001). Main cost drivers were inpatient care, psychiatrists and psychotherapists. Mood, anxiety, substance use disorders and obesity were significantly more frequent in ADHD patients and additional costs resulting from the comorbid conditions amounted up to €2800. Costs were slightly higher in women than men and increased with age for both genders. In young adults (18–30 years) health care costs dropped notably, especially costs for the medical treatment of ADHD with stimulants and costs for psychiatrists, before rising again in the group of patients over 30 years who had higher comorbidity rates.

Medical costs for ADHD are substantial, in part through frequently occurring comorbid conditions, and particularly in adulthood, and are likely to further accelerate in the coming years. A gap of care was found, starting with the transition age group of patients over 17 years, as indicated by reduced costs per person during young adulthood, as well as an overall strong drop in administrative prevalence. In the future, approaches to improve the situation of care and reduce costs at the same time, i.e. through managed care programmes, should be implemented and benefit from detailed knowledge on age and gender-specific cost-drivers.

Sleep alterations are frequent occurrence in Bipolar Disorder (BD), both in acute and interepisodic phases. Sleep alterations have been also described both long before BD onset, as aspecific risk syndromes, or as immediate prodromes of BD onset. The aim of the present study is to systematically review the relationship between sleep alterations anticipating for the full-blown onset of BD, both in general and according to specific polarities of onset.

A systematic literature research according to PRISMA statement and considering: 1. prospective studies about BD patients’ offspring with sleep alterations who later developed BD. 2. prospective studies assessing patients with sleep disorders who later developed BD. 3. retrospective studies on BD patients where sleep alterations before BD onset of the disease were reported.

A total of 16 studies were included in this review. Sleep disturbances may frequently appear 1 year before the onset of BD or more, often during childhood or adolescence. A decreased need for sleep may precede the onset of the illness, specially a manic episode, while insomnia appears to anticipate either a manic or a depressive episode. Hypersomnia seems to precede bipolar depressive episodes.

Sleep alterations frequently appear long before the onset of BD, and appear to be related specifically to the polarity of the index episode. The detection and treatment of sleep alterations in special high risk populations may help achieving an earlier detection of the illness.

Brain structural connectome comprise of a minority of efficiently interconnected rich club nodes that are regarded as ‘high-order regions’. The remission of major depressive disorder (MDD) in response to selective serotonin reuptake inhibitor (SSRI) treatment could be investigated by the hierarchical structural connectomes’ alterations of subnetworks.

Fifty-five MDD patients who achieved remission underwent diffusion tensors imaging (DTI) scanning from 3 cohorts before and after 8-weeks antidepressant treatment. Five hierarchical subnetworks namely, rich, local, feeder, rich-feeder and feeder-local, were constructed according to the different combinations of connections and nodes as defined by rich club architecture. The critical treatment-related subnetwork pattern was explored by multivariate pattern analysis with support vector machine to differ the pre-/post-treatment patients. Then, relationships between graph metrics of discriminative subnetworks/ nodes and clinical variables were further explored.

The feeder-local subnetwork presented the most discriminative power in differing pre-/post- treatment patients, while the rich-feeder subnetwork had the highest discriminative power when comparing pre-treatment patients and controls. Furthermore, based on the feeder connection, which indicates the information transmission between the core and non-core architectures of brain networks, its topological measures were found to be significantly correlated with the reduction rate of 17-item Hamilton Rating Scale for Depression.

Although pathological lesion on MDD relied on abnormal core organization, disease remission was association with the compensation from non-core organization. These results suggested that the dysfunctions arising from hierarchical subnetworks are compensated by increased information interactions between core brain regions and functionally diverse regions.

Little is known about the association between trauma and intellectual disability in SMI patients.

To establish the prevalence of trauma and its association with intellectual functioning in SMI outpatients.

A cross-sectional study was conducted in two mental health trusts in the Netherlands. We used the Trauma Screening Questionnaire (TSQ) to screen for trauma and PTSD, and the Screener for Intelligence and Learning disabilities (SCIL) for suspected MID/BIF. Chi-square and t-tests were used to test differences in outcome over patient characteristics. Post-hoc analysis was used to investigate gender differences between patients with and without MID/BIF on trauma and sexual trauma.

Any trauma was found in 86% of 570 patients and 42% were suspected for PTSD. The SCIL suggested that 40% had Borderline Intellectual Functioning (BIF), half of whom were suspected of having Mild Intellectual Disability (MID). These patients had more traumatic experiences (1.89 in BIF, 1.75 in MID, against 1.41 in SCIL-negative patients). Female MID/BIF patients (61%) had experienced significantly more sexual abuse than male MID/BIF patients (23%).

Significantly more SMI outpatients who screened positive for MID/BIF reported having experienced traumatic events than those who screened negative. Rates of all trauma categories were significantly higher in the screen-positive group, who were also more likely to have PTSD. Sexual abuse occurred more in all females but the SCIL positive women are even more often victim. Clinical practice has to pay more attention to all of these issues, especially when they occur together in a single patient.

The predictive accuracy of the Clinical High Risk criteria for Psychosis (CHR-P) regarding the future development of the disorder remains suboptimal. It is therefore necessary to incorporate refined risk estimation tools which can be applied at the individual subject level. The aim of the study was to develop an easy-to use, short refined risk estimation tool to predict the development of psychosis in a new CHR-P cohort recruited in European country with less established early detection services.

A cohort of 105 CHR-P individuals was assessed with the Comprehensive Assessment of At Risk Mental States12/2006, and then followed for a median period of 36 months (25th-75th percentile:10–59 months) for transition to psychosis. A multivariate Cox regression model predicting transition was generated with preselected clinical predictors and was internally validated with 1000 bootstrap resamples.

Speech disorganization and unusual thought content were selected as potential predictors of conversion on the basis of published literature. The prediction model was significant (p < 0.0001) and confirmed that both speech disorganization (HR = 1.69; 95%CI: 1.39–2.05) and unusual thought content (HR = 1.51; 95%CI: 1.27–1.80) were significantly associated with transition. The prognostic accuracy of the model was adequate (Harrell’s c- index = 0.79), even after optimism correction through internal validation procedures (Harrell’s c-index = 0.78).

The clinical prediction model developed, and internally validated, herein to predict transition from a CHR-P to psychosis may be a promising tool for use in clinical settings. It has been incorporated into an online tool available at: https://link.konsta.com.pl/psychosis. Future external replication studies are needed.

A large variation in cognitive performance exists between European regions. However, it is unclear how older Europeans differ in the rate of cognitive decline.

We analysed data from 22 181 individuals (54% women; median age 71) who participated in the Survey on Health, Ageing and Retirement in Europe. Cognition was measured using tests on verbal fluency, immediate and delayed recall. We used linear regression and linear mixed effects regression to examine regional differences in the level of cognitive performance and the rate of cognitive decline.

Scandinavians had the highest baseline cognitive scores (mean standardized overall cognitive score 0.3), followed by Western Europeans (mean 0.2), Central and Eastern Europeans (mean 0.1) and individuals from Mediterranean countries (mean -0.4). These differences persisted even after adjustment for sociodemographic and clinical characteristics. The annual cognitive decline in Scandinavia (0.59%) was approximately two times greater than in Western Europe (0.28%), Central and Eastern Europe (0.25%) and Mediterranean countries (0.23%).

There are substantial differences in cognitive performance as well as rates of cognitive decline among the elderly throughout European regions. This might be explained by differing levels of cognitive reserve.