The work presented was funded by the Dutch ministry of Infrastructure and transport and the European Committee.

The author declares that he has no competing interest.

The author declares that he has no competing interest.

The author declares that he has no competing interest.

The author declares that he has no competing interest.

Although not included in current diagnostic systems, deficit versus non-deficit and resistant versus non-resistant schizophrenia subtypes look more promising than traditional schizophrenia subtypes in terms of stability across time, clinical utility and interest for research.

To critically analyze evidence supporting the validity of two schizophrenia subtypes: Deficit Schizophrenia (DS) and Treatment Resistant Schizophrenia (TRS).

Empirical data supporting the validity of DS and TRS subtypes will be critically reviewed.

DS, in comparison with non-deficit schizophrenia, is characterized by poorer premorbid functioning, more insidious onset, lower prevalence of dysphoria, hostility, suicidal ideation, depressive symptoms and substance abuse, different neurobiological abnormalities, and poorer response to treatment. The diagnosis of DS shows high reliability and stability across time. However, research based on this approach has proven difficult, especially in first-episode schizophrenia, and findings have not been as homogeneous as expected.

TRS patients, as compared to non-TRS ones, show persisting psychotic symptoms, greater severity of negative symptoms, more severe cognitive dysfunctions, poorer premorbid functioning, longer duration of untreated psychosis, more frequent co-morbidity with personality disorders, earlier illness onset and poorer social functioning.

Future research should consider a) refining diagnostic criteria for DS and identifying valid DS endophenotypes; b) dissecting TRS based on psychopathological characteristics (e.g. presence of primary and persistent negative symptoms or persistently severe positive symptoms), and underlying neurobiological mechanisms (e.g. dopamine synthesis capacity and glutamatergic transmission).

SG received honoraria or Advisory board/consulting fees from the following companies: Lundbeck, Janssen Pharmaceuticals, Hoffman-La Roche, Angelini-Acraf, Otsuka, Pierre Fabre and Gedeon-Richter. All other authors have declared.

The DS was identified using the SDS. The MMP-9, BDNF, and COMT gene polymorphisms were genotyped. DNA methylation of the human endogeneous retrovirus type K (HERV-K) sequences was determined. Smell identification test was performed using the Sniffin’ Sticks test. For the assessment of executive function we used the Wisconsin Card Sorting Test, the Trail Making Test, Verbal Fluency Test Phonemic, Stroop Color Word Test and Go/No Go task.

There was no association between the examined functional gene polymorphisms, methylation levels and DS. Similarly, there was no relationship between overall odor identification abilities and the deficit/non-deficit dichotomy. The results tended to indicate specific problems in the identification of few odors in DS. DS, compared with the non-deficit group, obtained lower scores in the WCST and TMT and exhibited greater interference within concept formation and non-verbal cognitive flexibility. Furthermore, in patients with the first schizophrenia-like episode, the number of circulating Lin (-)/CD45 (-)/CD34 (+) very small embryionic like stem cells (VSELs) and the S1P plasma level were the best predictors of risk and are proposed as novel markers for the first “schizophrenic” episode of psychosis.

The authors declare that they have no competing interest.

The author declares that he has no competing interest.

The author has not supplied his declaration of competing interest.

Lifetime prevalence of psychiatric comorbidity in neurological patients is as high as 55%, but it remains often undetected and therefore untreated in hospital settings. Further, clinicians tend to make little use of the consultative and liaison psychiatric team for detection and treatment of anxiety and mood disorders in neurological patients. The current study aimed to investigate whether the implementation of a stepped screening protocol with high risk feedback to the clinician had an influence on the use of consultative and liaison psychiatric services.

All patients admitted to the neurological ward were assessed using a stepped screening protocol for depression, anxiety and substance use during 15 months. Positive screening resulted in feedback to the clinicians depending on the study phase (e.g. feedback vs. no feedback).

No differences were found in the use of consultative and liaison psychiatric services during the non-feedback and feedback phase.

Screening and high risk feedback of psychiatric comorbidity in neurological patients does not increase psychiatric referral rates. It points to the necessity of a more integrated collaborative care model for detection and treatment of psychiatric comorbidity.

The authors have not supplied their declaration of competing interest.

Inflammatory mediators may be relevant to explain the frequent comorbidity between depression, neurocognitive disorders and HIV. HIV induces activation of inflammatory mediators, mainly cytokines, that have been involved in the onset of depression and response to antidepressant treatment.

To identify recurring profiles of inflammatory biomarkers subtending depression, effectiveness of antidepressants and neurocognitive disorders among HIV-infected individuals.

All adult newly HIV-diagnosed out-patients attending HIV clinics in three towns of Northern Italy were screened, assessed for depression and studied immunologically and for neurocognitive disorders.

Twenty-five patients have been enrolled so far: of these, 35% were positive to PHQ-9 screening, of which 6 were positive to the diagnostic assessment for depression. No neurocognitive disorders were found among the patients. As the project will develop, it is expected that frequency of depression, neurocognitive disorders and effective antidepressant treatment will be found to correlate to the profile of immune biomarkers. These findings might help to understand the etiology of depression in HIV, and specifically the role of inflammation and immunological changes.

The authors have not supplied their declaration of competing interest.

The author has not supplied his declaration of competing interest.

The author has edited and co-authored a book on “Women in Academic Psychiatry: A mind to Succeed”

The author has not supplied his declaration of competing interest.

Attention deficit/hyperactivity disorder (ADHD) is an important contributing factor in the pathophysiology of substance use disorders (SUD), and ADHD occurs more often in populations with SUD compared to the general population. This high prevalence rate and comorbidity may relate to a shared neurobiological vulnerability, including a deregulation of the brain's dopamine system. This comorbidity directly impacts the treatment of ADHD: treatment with methylphenidate is less effective in patients with ADHD and SUD compared to ADHD patients without SUD.

We investigate the underlying neurobiological background of reduced treatment effectiveness for adult ADHD patients with comorbid SUD.

We observed lower available dopamine transporters, as well as a reduced binding of methylphenidate to these transporters, and more neurocognitive dysfunction in adults ADHD patients with SUD compared to ADHD patients without SUD.

Comorbid ADHD and SUD has a high prevalence rate and reduces ADHD treatment effectiveness, which makes it necessary to screen for the presence of ADHD in patients seeking SUD treatment. Neurobiological and neurocognitive differences are present between ADHD patients with and without SUD, which together may partially explain the reduced effectiveness of methylphenidate in adult ADHD patients with SUD.

The author has not supplied his declaration of competing interest.

Adults with ADHD describe self-medicating with cannabis, with some reporting a preference for cannabis over ADHD medications.

The experimental medicine in ADHD-cannabinoids study was a pilot randomised placebo-controlled experimental study of a cannabinoid medication, Sativex oromucosal spray, in 30 adults with ADHD.

The primary outcome was cognitive performance and activity level using QbTest. Secondary outcomes included ADHD and emotional lability (EL) symptoms.

Thirty participants were randomly assigned to the active (n = 15) or placebo (n = 15) group. For the primary outcome, no significant difference was found in the ITT analysis although the overall pattern of scores was such that the active group usually had scores that were better than the placebo group (Est = -0.17, 95%CI-0.40 to 0.07, P = 0.16, n = 15/11 active/placebo). For secondary outcomes, Sativex was associated with non-significant improvements in hyperactivity/impulsivity (P = 0.03), a cognitive measure of inhibition (P = 0.05), inattention (P = 0.10) and emotional lability. Per-protocol effects were higher.

Results did not meet significance following adjustment for multiple testing. One serious (muscular seizures/spasms) and three mild adverse events occurred in the active group and one serious (cardiovascular problems) adverse event in the placebo group. Adults with ADHD may represent a subgroup of individuals who experience a reduction of symptoms and no cognitive impairments following cannabinoid use. This provides some preliminary evidence in support of the self-medication theory of cannabis use in ADHD. A larger trial is warranted.

Kings College London research support account for Asherson received honoraria for consultancy to Shire, Eli-Lilly and Novartis educational/research awards from Shire, Lilly, Novartis, Vifor Pharma, GW Pharma and QbTech speaker at sponsored events for Shire, Lilly and Novartis.

Despite the high prevalence of ADHD in adults with SUD and the availability of an approved guideline, under diagnosis and inadequate treatment still persist. This comorbidity associates with reduced treatment effectiveness, making successful treatment in adults with ADHD and SUD a challenge.

The guideline of 2010 for recognizing and treating adult ADHD in patients with SUD is updated in 2016, in cooperation with caregivers, of the addiction centers in Belgium and based on research literature and clinical experience. The english translation is discussed by an international group of clinicians and experts to result in a consensus statement via ICASA (International Collaboration on ADHD and Substance Abuse).

This consensus presents a useful guide for the diagnosis and treatment of ADHD and SUD. Due to the lack of scientific evidence on some of the topics, the guide is a combination of evidence based and practice based recommendations.

The management of ADHD in patients with SUD remains a challenge. Diagnosis is complicated by SUD symptoms and by the skepticism associated with the recognition of ADHD in adults. The treatment is hampered by high relapse rates and reduced effectiveness of the currently available pharmacotherapies. Combining psycho-and pharmacotherapy in an integrated treatment that covers both ADHD and SUD, may help to keep these patients in treatment.

A Dutch manual for the integrated treatment of ADHD and SUD is being developed.

Honorarium Lilly.

Advisory board Johnson&Johnson.

The author has not supplied his declaration of competing interest.

It's known that psychiatric disorders are caused to either environmental and genetics factors. Through the years several hypotheses were tested and many genes were screened for association, resulting in a huge amount of data available for the scientific community. Despite that, the molecular mechanics behind psychiatric disorders remains largely unknown. Traditional association studies may be not enough to pinpoint the molecular underpinnings of psychiatric disorder. We tried to applying a methodology that investigates molecular-pathway-analysis that takes into account several genes per time, clustered in consistent molecular groups and may successfully capture the signal of a number of genetic variations with a small single effect on the disease. This approach might reveal more of the molecular basis of psychiatric disorders.

i)We collected data on studies available in literature for the studied disorder (e.g. Schizophrenia, Bipolar Disorder);ii)We extracted a pool of genes that are likely involved with the disease;iii)We used these genes as starting point to map molecular cascades function-linked. The molecular cascades are then analyzed and pathways and sub-pathways, possibly involved with them, are identified and tested for association.

We obtained interesting results. In particular, signals of enrichment (association) were obtained multiple times on the molecular pathway associated with the pruning activity and inflammation. Molecular mechanics related to neuronal pruning were focused as a major and new hypothesis for the pathophysiology of psychiatric disorders and the role of inflammatory events has been extensively investigated in psychiatry. intersting, inflammatory mechanics in the brain may also play a role in neuronal pruning during the early development of CNS.

The author has not supplied his declaration of competing interest.

Cognitive dysfunction is recognized as a core feature of schizophrenia and is considered an important predictor of functional outcomes. Despite this, current treatment strategies largely fail to ameliorate these cognitive impairments. In order to develop more efficient treatment strategies, a better understanding of the pathogenesis of cognitive dysfunction is needed. Accumulating evidence indicates that genetic risk of schizophrenia contributes to cognitive dysfunction. However, the precise genetic variants jointly influencing schizophrenia and cognitive function remain to be determined.

Here, we aimed to identify gene loci shared between schizophrenia and general cognitive function, a phenotype that captures the shared variation in performance across several cognitive domains.

Using a Bayesian statistical framework, we compared genome-wide association study (GWAS) data on schizophrenia from the Psychiatric Genomics Consortium cohort (n = 79,757) with GWAS data on general cognitive function from the CHARGE Consortium (n = 53,949). By conditioning the false discovery rate (FDR) on shared associations, this statistical approach increases power to detect gene loci.

We observed substantial polygenetic overlap between schizophrenia and general cognitive function, which replicated across independent schizophrenia sub-studies. Using the conditional FDR approach we increased discovery of gene loci and identified 13 loci shared between schizophrenia and general cognitive function. The majority of these loci (11/13) shows opposite directions of allelic effects in the phenotypes, in line with previous genetic studies and the observed cognitive dysfunction in schizophrenia.

Our study extends the current understanding of the genetic etiology influencing schizophrenia and general cognitive function by identifying shared gene loci between the phenotypes.

The authors have not supplied their declaration of competing interest.