Negative symptoms in schizophrenia are present both in behavior and in the subjective experiences of the patients. However the latter are not represented in most rating instruments.

To review assessment methods for the subjective experiences of primary negative and related symptoms in schizophrenia.

Literature review and comparison of negative symptoms as judged by the rater with reports of self experiences.

The Scale for Assessment of Negative Symptoms (SANS) is an instrument concerning the positive-negative distinction in schizophrenia. The SANS is based on the judgment of the rater about the behavior of the patient. Items reflecting subjective experiences of the patients were initially included in the SANS, buy they were not significantly correlated with the behavioral items, and were therefore excluded from this scale by its author.

Huber's group emphasized subjective experiences in schizophrenia. According to this concept the lack of behavioral negative symptoms does not exclude subjective experiences of deficiencies (part of „basic symptoms”, „pure defect”). Nineteen such symptoms were included in the Subjective Deficit Syndrome Scale (SDSS).

We compared negatives symptoms measured by SANS with the corresponding subjective experiences measured by SDSS in patients with the diagnosis of schizophrenia and schizoaffective disorder (n = 122).

D2 receptor occupancy during antipsychotic treatment was found to be associated with subjective experiences/well being, which can be assessed with specific rating scales (e.g.: Drug Attitude Inventory and Subjective Well-Being under Neuroleptic Treatment).

Behavioral symptoms and the subjective experiences of the negative syndrome are not correlated with each other.

Remission, both symptomatic and psychosocial, is now an achievable goal in a substantial proportion of schizophrenia patients.

to develop a brief, clinician rated scale for the assessment of psychosocial remission in schizophrenia (the PSRS). The scale is to match the quantification of symptomatic remission as delineated by the American Psychiatric Association (APA) task force.

a “bank” of 124 questions pertaining to psychosocial remission was derived from published scales reflecting two domains: quality of life (QoL) and activities of daily living (ADL). Psychiatrists, residents, psychiatric nurses and community nurses were presented with the questions. All were asked to choose the 8 items they considered as reflecting the essence of psychosocial remission. Inter-rater reliability of the final scale version was assessed amongst psychiatrists.

the questions' “bank” was reviewed by 429 mental health professionals. The four items found to be most frequently sanctioned in the QoL domain were: a. familial relations (endorsed by 78% of participants), b. understanding and self-awareness (46%), c. energy (58%) and d. interest in every-day life (38%). The four items sanctioned in the I-ADL domain were: a. self-care (86%), b. activism (65%), c. responsibility for medications (54%) and d. use of community services (32%). Inter-rater reliability amongst 70 psychiatrists ranged from 0.67 to 0.83.

the PSRS is an 8-item scale quantifying psychosocial remission in schizophrenia in a manner that complements symptomatic assessment of remission. The PSRS may be useful for both research and clinical evaluation.

Juvenile sex offending all too often is the reason of public commotion and concern. About 20% of all rapes and 20–50% of cases of child abuse are perpetrated by juveniles. However little is known on the psychiatric characteristics and recidivism rates of these youths. In the present study the prevalence of psychopathology in (subgroups of) juvenile sex offenders and its relation with criminal recidivism two to four years later were investigated.

Semi-structured psychiatric interviews (K-SADS-PL) and a parent-report questionnaire (CSBQ) were carried out with 106 adolescent sex offenders (mean age 15.0 ± 1.5 years, 60 group offenders, 27 solo rapists, and 19 child molesters) referred to the Dutch child protection agency and juvenile justice institutions. Recidivism was ascertained from registration systems.

Three quarters of juvenile sex offenders met criteria for at least one psychiatric disorder and comorbidity was found in more than half of the subjects. Child molesters showed the highest rates of internalizing disorders and showed most pronounced autism spectrum disorder core symptomatology. Forty percent of juvenile sex offenders had committed multiple sexual offenses, but none recidivated sexually within the 2–4 years after the study. Compared to one time sex offenders, multiple sex offenders were higher in DBD and anxiety disorder.

Child and adolescent psychiatric care should be given to juvenile sex offenders, with particular attention to multiple sex offenders and child molesters. However, the predictive value of psychopathology for sexual recidivism remains unclear and warrants further research.

Considering bipolar depression a diagnostic and therapeutic challenge, distinct from unipolar depression and associated with significant morbidity and mortality, we aim to systematically review guidelines, consensus meetings and treatment algorithms on the acute treatment of bipolar depression to critically underline the role of mood-stabilizers.

The MEDLINe/PubMed/Index Medicus, PsycINFO/PsycLIT, Excerpta Medica/EMBASE, databases were searched using “depression”, “bipolar”, “mood-stabilizers”, “manic-depressive” and “treatment guidelines” as key words since 2005 onward.

Among mood-stabilizers, the use of lamotrigine is overall recommended as first-line choice. Monotherapy is suggested on the basis of several positives clinical trials, however, pooled data analysis showed that lamotrigine was only modestly useful. Valproate monotherapy is suggested as first-line treatment option in the WFSBP and BAP guidelines, and in combination with lithium or antidepressants, but it is not mentioned among first-line choices neither in monotherapy nor as adjunctive treatment in two guidelines (ICG, NICE).

Lithium monotherapy is suggested in three of all guidelines (ICG, BAP, CANMAT and ISBD) as first-line treatment on the basis of positive evidence, but it is not recommended as first-choice by WFSBP and NICE guidelines. Its combination with lamotrigine, valproate and other agents is instead recommended as first choice treatment.

In summary, mood-stabilizers are considered a key point in the management of bipolar depression, preferably in combination. Despite algorithms evidence-based could be helpful to guide clinicians, they always need the case by case pharmacotherapeutic consideration.

Recent advances in DNA sequencing have allowed large neuropsychiatric populations to be screened for genetic variants that may influence the progression of mental disorders. Recent GWAS (Genome Wide Association Studies) have identified risk loci for schizophrenia (SZ), Bipolar disorder (BD) and Alzheimer's disease (AD). Objectives

A major concern is to understand how these recently identified risk variants influence vulnerability to neuropsychiatric disorders.

Common risk variants may contribute to intermediate phenotypes associated with neuropsychiatric disorders. A key aim is to investigate whether individuals expressing susceptibility loci demonstrate similar deficits to those of patients. This may help to elucidate new pharmacological pathways.

A combination of neuroimaging (fMRI & EEG) and behavioural studies (emotional working memory task, visual encoding efficiency and decision-making ability) were used to probe risk carriers for GWAS validated risk loci associated with SZ, BD and AD. The paradigms were previously validated as methods that neuropsychiatric populations displayed deficits in.

GWAS risk SNP carriers displayed patterns of behavioural/neurophysiology typically seen in their respective neuropsychiatric populations. The risk carrier populations display less overt phenotypes than patients or first-degree relatives, nevertheless displayed small but significant trait effects typically observed in individuals with high levels of genetic risk.

GWAS risk carriers display small but significant effects that reflect a sub-clinical phenotype typically seen in individuals with high genetic risk. Imaging techniques such as fMRI are useful in measuring these subtle differences. Behavioural testing requires larger populations or more penetrant risk alleles for overt phenotypic effects to be witnessed.

The underlying neurobiology of major depressive disorder (MDD) is likely to represent an interaction between genetic susceptibility and environmental factors like stress. There is growing evidence that epigenetic processes might mediate the effects of the social environment during childhood on gene expression.

We investigated in multimodal high-resolution MRI-genetic studies whether microstructural and functional brain changes are the result of gene-environment interactions.

Patients with major depressive disorder (MDD), high-risk subjects for developing MDD and healthy participants were investigated using high-resolution magnetic resonance imaging (MRI), high angular resolution diffusion imaging (HARDI) and functional MRI. Furthermore, we assessed early life adversity and measured the serotonin transporter polymorphisms (5-HTTLPR).

We demonstrated that patients with MDD have smaller hippocampal and frontal cortex volumes associated with gen-environment interactions. Healthy Subjects at risk for developing depression, who manage to stay healthy, show better activation of the frontal cognitive control system. Those who had stronger fibre connections between frontal and temporal brain regions also better managed incidences of adversity in early life.

Stress x gene interactions seem to account for at least some of the structural brain changes. Resilience against environmental stressors might be associated with stronger neural fibre connections and more effective cognitive control networks.

To determine predictors of transition from ultrahigh risk into psychosis.

The Dutch EDIE trial has included 201 people with an ultrahigh risk for psychosis. These were included with both a referral based strategy and a screening all help-seeking people strategy. The study had a 24 month inclusion period and an 18 mont follow-up period with each patient. The preliminary results are presented.

A loogistic regression was performed over 164 cases. 29 patients developed a psychosis.

Predictor variables were depression, social intercation anxiety, positive symptoms on the CAARMS, negative symptoms on the CAARMS, quality of life, social functioning, genetic risk, and the personal beliefs about illness.

The backward logistice regression (likelyhood ratio) discarded four variables. Predictors of psychosis were depression, positive symptoms, genetic liability and beliefs about illness at basline.

People with hihd scores on depression and positive symptoms are likely to develop a psychosis. Also those who have a psychotic parent and positive symptoms a more lekly to make a transition. Interestingly people that consider their condition as hopeless, feel entrapped by their condition, excluded by other pople and not in control of symptoms also have a heightened chance for developing psychosis in this sample.

Individuals at Ultra High Risk (UHR) for psychosis typically present with attenuated psychotic symptoms. However it is difficult to predict which individuals will later develop frank psychosis when their mental state is rated in terms of individual symptoms.

The objective of the study was to examine the phenomenological structure of the UHR mental state and identify symptom profiles that predict later transition to psychosis.

Psychopathological data from a large sample of UHR subjects were analysed using latent class cluster analysis.

A total of 318 individuals with a UHR for psychosis. Data were collected from two specialised community mental health services for people at UHR for psychosis: OASIS in London and PACE, in Melbourne.

Latent class cluster analysis produced 4 classes: Class 1 - Mild was characterized by lower scores on all the CAARMS items. Subjects in Class 2 - Moderate scored moderately on all CAARMS items and was more likely to be in employment. Those in Class 3 - Moderate-Severe scored moderately-severe on negative symptoms, social isolation and impaired role functioning. Class 4 - Severe was the smallest group and was associated with the most impairment: subjects in this class scored highest on all items of the CAARMS, had the lowest GAF score and were more likely to be unemployed. This group was also characterized by the highest transition rate (41%).

Different constellations of symptomatology are associates with varying levels of risk to of transition to psychosis.

Stress is a key feature of many aetiological models of psychosis and there is considerable empirical evidence implicating stress in the development of psychosis. This paper investigates the role of psychosocial stress in the onset of psychosis by examining the relationship between current and lifetime exposure to traumatic experiences and psychosocial stressors, HPA axis function, and psychopathology in people at high risk of developing psychosis.

Sixty ‘high risk’ (HR) participants were compared with 50 healthy control (HC) participants on measures of exposure to psychosocial stressors. Subgroups of HR and HC participants which provided saliva samples were compared regarding measures of HPA axis function.

HR participants were exposed to greater levels of psychosocial stress than HC participants. Specifically, HR participants were more likely to have been separated from their parents (p = .003), report severe parental antipathy (p = .011), and have been bullied while growing up (p = .024). HR participants experienced greater levels of perceived stress than HC participants (p = .001) and were more likely to have had a negative life event in the previous 6 months (p < .001). Positive correlations were found between current stress and number of life events and attenuated psychotic symptoms (r = .585, p < .001, and r = .384, p = < .001, respectively) in the HR participants.

This study shows that people at high risk of developing psychosis experience greater levels of psychosocial stress than matched healthy control participants throughout the lifetime, from early childhood to the present day, and that current stress is strongly associated with psychotic symptomatology.

Potentially chronic diseases often have a critical point in their course beyond which treatment becomes less effective. In support of this, early treatment in schizophrenia and other psychoses has been linked to better outcome.

The emergence of simultaneous brain volume changes in those ultra-high-risk individuals who develop psychosis indicate an active biological process, and underline the importance of pre-onset treatment. However, pre-psychotic intervention has also been questioned as, using current criteria, only 20–50% of individuals classified as prodromal develop a psychotic disorder within a 1–2 years period.

Treatment agents in the pre-psychotic phase should, therefore, not have major side effects. Bioactive lipids are molecules that have both intra- and intercellular roles, including mediation, modulation and control of neurobiological processes, such as ion channel and receptor activity, neurotransmitter release, synaptic plasticity, second messenger pathways and neuronal gene expression.

Long-chain omega-3 polyunsaturated fatty acids (PUFAs) have been shown effective for both, mood and psychotic symptoms, and they have neuroprotective properties. Because of the controversy concerned with the extent to which an intervention may produce harm which outweighs its benefits, omega-3 PUFAs are prime candidates for evaluation in putatively prodromal individuals.

We report on the first randomized, placebo-controlled trial on the preventive use of omega-3 fatty acids in 81 ultra-high-risk individuals.

Supplementation with long-chain omega-3 PUFAs reduces the risk of progression to psychotic disorder, and offers a safe and efficacious strategy for indicated prevention in individuals at ultra-high-risk of developing a psychotic illness.