Even though Attention Deficit Hyperactivity Disorder is estimated to be 70-90% heritable, full understanding of the etiology of this disorder must be framed under a bio-ecological developmental model that contemplates the gene/environment interaction as a matrix of risk/resilience factors. Family psychosocial variables, parenting stress and parental discipline have been identified as environmental risk factors related to the course of the disorder. However there is a lack of research exploring causality and interrelations between these variables and ADHD. This was the aim of the present study, to investigate the effect of family environment in the onset and course of ADHD.

One hundred and fourteen families with children with ADHD participated in the study. Parents completed a Semi-Structured Interview, the Parenting Stress Index Questionnaire (Abidin 1990) and The Parenting Scale (Arnold, O'Leary, Wolff, & Acker, 1993) that measures parents’ dysfunctional discipline practices.

Structural equation analysis was fitted to the relation of family variables and ADHD. The analysis showed interrelationship among family psychosocial variables, parenting stress and discipline practices.

Although future research should make use of longitudinal design to untangle the issues of causal directions between these constructs and potential transactional processes, our findings evidence that interventions in ADHD should incorporate a parenting training component focused on behaviour management strategies and on effective dimensions of parenting.

It is widely believed that comorbid personality disorders (PDs) have a negative influence on the effects of treatment for axis-1 anxiety disorders. However, many studies reporting negative influences suffer from methodological problems, such as inference of PD after treatment by clinical judgement. The aim of our studies was to investigate the influence of comorbid PDs on outcome of CBT for anxiety disorders in a double blind prospective design.

Axis-1 and axis-2 disorders were assessed with SCID interviews. Therapists and patients were blind for outcome of SCID-II interview. Patients received state of the art CBT for their main anxiety disorder. We controlled for baseline levels. Outcome was assessed with Fear Questionnaire and SCL-90.

In a very large sample of more than 1800 patients we didn't find evidence for a negative influence of comorbid PDs. The only effect we found was that comorbid borderline PD was associated with drop-out. In a smaller sample (N = 398) we found evidence that PDs predicted higher avoidance levels after treatment, but no other psychopathology. Interestingly, specific beliefs related to PDs, notably mistrust and dependency beliefs, were related to higher symptom levels after treatment.

The influence of PDs on CBT of anxiety disorders is not strong. When effects were found, they were very small. Two cognitive beliefs seem to be central in interference of PDs with CBT: mistrust and dependency related beliefs.

The Danish Longitudinal Study on Alcoholism was designed to identify predictors of adult male alcoholism. The present study examines the predictability of premorbid personality disorders.

Subjects were selected from a Danish birth cohort (n = 9125, born 1959 – 61) that included 223 sons of alcoholic fathers (high risk = HR) and 106 matched sons of non-alcoholics (low risk = LR). These subjects have been studied systematically over the past 40 years. Most recently, they were evaluated at age 40 (n = 202) by a psychiatrist using structured interviews and DSM-III-R criteria to diagnose an Alcohol Use Disorder.

HR subjects were more likely than LR subjects to develop alcohol dependence over the past 40 years (31% vs. 16%, p < .03). However, HR subjects were not more likely to develop alcohol abuse (17% vs. 15%). Both ADHD (as measured by school teachers) and ASPD (onset before age 15) predicted alcoholism independently at age 40. ADHD and ASPD were much stronger independent predictors of adult alcoholism than parental risk status. Other personality and anxiety disorders did not predict an alcoholic outcome.

Paternal alcoholism predicted alcohol dependence in sons at age 40. But the most predictive premorbid variables were ASPD and ADHD, both with onset in childhood and adolescence.

Very little is known about the impact of manic post-partum episods (MPPE) and mother-baby interactions.

The objective of this preliminary work was to compare mother-baby interactions of mothers hospitalized for MPPE with the baby, and mother-baby interactions of mothers recruited in the community.

Interactions between 20 MPPE mothers and their babies aged between 2-6 months, and 13 community mothers and their babies (2-6 months), were evaluated with the «Global Rating Scales of Mother-Infant Interaction».

MPPE mothers were more intrusive than community mothers. The MPPE babies were more withdrawn than community babies.

More research is needed to evaluate the long term impact of such pattern of early interactions.

Neurocognitive deficits and schizotypal features are elevated in first-degree relatives of schizophrenia patients. However, the co-aggregation of these indicators is not well known. Some studies have found that neurocognitive deficits and schizotypy increase in severity with the density of family history of schizophrenia. Therefore, we studied in affected families a) whether the status of Presumed Carrier (PC) of the genetic risk for schizophrenia is associated with higher levels of neurocognitive deficits and schizotypic features and b) the relationship between schizotypy and neurocognition.

From an ongoing Catalan Multicentric Family Study on Schizophrenia, 70 families were included in this analysis. 90 non-psychotic parents of schizophrenic patients (age 50.7/8.8; education 10.3/4.04; IQ 96.2/14.6) were defined as PC if they had at least one first (apart of offspring) or second degree relative with schizophrenia spectrum disorders (FIGS), resulting in 17 PC and 73 non-PC. Schizotypic features were assessed with the SCID-II and the SPQ-B. Working memory (WM), executive functioning, sustained attention, verbal fluency and logical memory were also assessed.

PC differed significantly from NPC on verbal working memory, even after controlling for IQ (d=0.8). They did not differ on any of the self-reported or interview measures of schizotypy. The negative schizotypic dimension was associated with more WCST-perseverative errors, and low scores in spatial-WM, verbal fluency and immediate/delayed logical memory.

A large association was found between verbal-WM and the familial background of schizophrenia. Only negative features were associated with some neurocognitive functions, supporting the view of multiple independent dimensions or a pleiotropic expression of risk.

Prospective studies of young individuals at high genetic risk of schizophrenia allow investigation of whether any neurodevelopmental abnormalities usefully predict the development of the disorder.

163 high risk subjects with an initial mean age of 21 years were recruited as they had at least two relatives with schizophrenia. Together with 36 control subjects, they were examined at baseline (with developmental, clinical, neuropsychological and structural/functional MRI measures) and at 18 month intervals thereafter. Comparisons were made between those who developed schizophrenia, well controls, a well high risk group and those of the high risk sample with partial or isolated psychotic symptoms.

21 high risk subjects developed schizophrenia within an average time of two and a half years. A much larger number have shown isolated or partial psychotic symptoms and the whole high risk sample differed from controls on several variables. Those who developed schizophrenia differed from those with psychotic symptoms who did not on several measures including: interview and self-report measures of schizotypy, the AVLT1-5, and fMRI-BOLD responses on three separate tasks.

Schizophrenia is a disorder which has its origins very early in life, but develops over years. Its mode of inheritance affects many more individuals than will develop the illness and partial impairment can be found in them. Highly significant predictors of the development of schizophrenia are detectable years before onset.

Aspects of cognitive function and schizotypy have been proposed as potential endophenotypes for schizophrenia. It is unknown if the expression of these endophenotypes at the population level is modulated by the genetic variability of candidate susceptibility genes for schizophrenia.

We examined the potential impact of 19 single nucleotide polymorphisms (SNPs) within five susceptibility genes for schizophrenia (COMT, DTNP1, NRG1, DAOA/G32 and DAAO genes) on cognition and self-rated schizotypy, in a representative population of 2,243 young male military conscripts. Single SNP and haplotype associations were evaluated.

Val carriers of the COMT val 158 met polymorphism, were associated with higher scores on the negative schizotypy factor, and a greater variability of response in attention capacity. DTNP1 SNPs rs2619522 and rs760761 exhibited several single marker associations, the minor alleles being associated with lower attention capacity but also a decrease in positive and paranoid schizotypy scores. DTNP1 haplotype load had borderline associations with non verbal IQ, paranoid schizotypy and sustained attention. For individual NRG1 polymorphisms, isolated but weak signals of association were noted with sustained attention and working memory, but not schizotypy. The risk allele of functional SNP8NRG243177 was associated with reduced spatial working memory capacity. An isolated effect of DAAO haplotype variability was noted on negative and disorganization schizotypy. No convincing association of DAOA/G32 variability was detected.

DTNP1 and val 158 met COMT, and less so NRG1 and DAAO variants, may exert gene-specific modulating effects on schizophrenia endophenotypes at the population level.

Psychosis is preceded by cognitive and physiological alterations. This may be useful in the risk assessment in subjects with putatively prodromal symptoms, and could contribute to better understand the temporal unfolding of the disease.

The early recognition and intervention program of the German Research Network on schizophrenia defines early and late prodromal stages according to psychopathological criteria. For concurrent and prospective validation of these risk stages, subjects undergo neurocognitive, electrophysiological and oculomotor assessments of putative vulnerability markers. About 125 early prodromal subjects (defined by the presence of basic symptoms, Klosterkoetter et al. 2001), and 90 late prodromal subjects (defined by attenuated positive symptoms or by brief occurrences of psychotic symptoms) have been assessed at inclusion.

As compared to psychiatrically healthy matched controls, late prodromals have significantly inferior verbal memory, verbal fluency, visual motor skills, and working memory. Impairments are qualitatively similar, but less pronounced in subjects in an early prodromal stage, with deficits of immediate verbal memory, verbal fluency and visuomotor performance being significant. Both groups show reduced auditory startle prepulse inhibition. Impairments are not correlated with depression and general distress scores, and are also largely independent of prodromal and attenuated positive symptoms. In early prodromals, global cognitive performance is related to the occurrence of psychotic symptoms during follow-up. Auditory P 300 is reduced in both prodromal groups, and predicts transitions to psychosis.

Neurocognitive and neurophysiological assessments validate and improve psychopathological risk assessment, and allow to disentangle stable vulnerability markers from indicators of imminent risk.

Funded by the German Federal Ministry for Education and Research BMBF (grant 01 GI 9934).

Cannabis has well established effects on cognitive processing but the neural basis of these is unclear. We used functional neuroimaging to investigate this, focusing on tasks that engaged verbal memory and response inhibition.

Subjects were 15 healthy males who had used cannabis < 25 times in their lifetime. Each subject was studied on 3 occasions, and was given either THC, CBD or placebo 1 hour prior to scanning, in a double-blind design. The order of drug administration was randomised and there was 1 month between each scanning session. During each session, images were acquired on a 1.5T GE camera while subjects performed a verbal paired associates memory task and a Go/No Go task. The modulatory effects of THC and CBD relative to placebo were examined by comparing activation during each task.

During the encoding phase of the memory task THC attenuated activation in the left temporal cortex compared to placebo. During the go-no go task, THC attenuated activation in the right inferior frontal cortex. Neither of these effects were attributable to differences in behavioural performance, sedation, or intoxication. The severity of psychotic symptoms provoked by THC was a function of its effect on right inferior frontal activation during response inhibition.

The effects of cannabis on verbal memory and motor control may be mediated through the influence of THC on left temporal and right inferior frontal activity, respectively. The induction of psychotic symptoms by cannabis may reflect an effect of THC on right inferior frontal activity.

The human endocannabinoid system interacts with various neurotransmitter systems and the endocannabinoid anandamide was found significantly elevated in CSF and inversely correlated to psychopathology (Giuffrida et al. 2004) providing a link to the neurobiology of schizophrenia. While delta-9-tetrahydrocannabinol, the psychoactive compound of Cannabis sativa, shows psychedelic properties, the major herbal cannabinoid compound cannabidiol was suggested recently a re-uptake inhibitor of anandamide. In addition potential antipsychotic properties have been hypothezised.

We performed an explorative, 4-week, double-blind, controlled clinical trial on the effects of purified cannabidiol in acute schizophrenia compared to the antipsychotic amisulpride. The antipsychotic properties of both drugs were the primary target of the study. Furthermore, side-effects and anxiolytic capabilities of both treatments were investigated.

42 patients fulfilling DSM-IV criteria of acute paranoid schizophrenia or schizophreniform psychosis participated in the study. Both treatments were associated with a significant decrease of psychotic symptoms after 2 and 4 weeks as assessed by BPRS and PANSS. However, there was no statistical difference between both treatment groups. In contrast, cannabidiol induced significantly less side effects (EPS, increase in prolactin, weight gain) when compared to amisulpride.

Cannabidiol proved substantial antipsychotic properties in acute schizophrenia. This is in line with our suggestion of an adaptive role of the endocannabinoid system in paranoid schizophrenia, and raises further evidence that this adaptive mechanism may represent a valuable target for antipsychotic treatment strategies.

The Stanley Medical Research Institute (00-093 to FML) and the Koeln Fortune Program (107/2000 + 101/2001 to FML) funded this study.