Findings from family, adoption and twin studies suggest that vulnerability to bipolar disorder follows a polygenic mode of inheritance with multiple genes, each of small effect, combining and contributing to the risk and the clinical expression of the disorder. The endophenotype approach has been proposed as a way to identify susceptibility genes in disorders with complex underpinnings. Endophenotypes are supposed to bridge the genotype to the clinical syndrome and to have a simpler genetic architecture than clinical diagnoses.

Our first aim is to confirm if cognitive measures are good potential endophenotypes. Therefore, we will examine the reliability and frequency of cognitive impairments in individuals with bipolar disorder and their biological relatives. The study of healthy relatives avoids confounding factors and should help identify potential endophenotypes.

We will also look for evidence linking particular cognitive impairments to specific genes on one hand and to the risk for bipolar disorder, on the other.

A literature review of articles published in 2008-2009 suggests that the genetic architecture of cognitive endophenotypes is more complex than initially predicted. In many published studies, no genetic association was found between cognitive deficits in bipolar disorder. We will try to understand the reasons and consequences of those disappointing results by analysing some methodological limitations, in particular regarding the statistical treatment of confounding factors.

We will also discuss theoretical considerations pointing out the fact that we may have been expecting too much and oversimplifying when supporting the idea that cognition is a less complex entity than bipolar disorder.

In summary, genetics, as well as foetal and early life environmental factors shape the size or capacity of our monoamine systems, of which the serotonergic one might play a leading role. Those constitutional properties then form the biological basis for personality traits, such as impulsiveness and “sensation seeking”, which interact with psychosocial settings and life events to form a pattern of reactivity to a current life event or psychosocial situation, shown as a high or low order of magnitude of gene-environment interaction. In the present paper emphasis is put on the role of genotypes of the serotonin transporter, of monoamine oxidases A and B, and of platelet monoamine oxidase B activity, which all have been shown to be of importance for behaviour and with obvious effects of interactions with environment. Under unfortunate circumstances constitutional properties might be strong enough to result in vulnerability for suicide, even with a modest influence of environment.

The etiology of suicide is complex in nature with both environmental and genetic causes that are extremely diverse. This extensive heterogeneity weakens the relationship between genotype and phenotype and as a result, we face many challenges when studying the genetic etiology of suicide. We are now in the midst of a genetics revolution, where genotyping costs are decreasing and genotyping speed is increasing at a fast rate, allowing genetic association studies to genotype thousands to millions of SNPs that cover the entire human genome. As such, genome-wide association studies (GWAS) are now the norm. In this article we address several statistical challenges that occur when studying the genetic etiology of suicidality in the age of the genetics revolution. These challenges include: (1) the large number of statistical tests; (2) complex phenotypes that are difficult to quantify; and (3) modest genetic effect sizes. We address these statistical issues in the context of family-based study designs. Specifically, we discuss several statistical extensions of family-based association tests (FBATs) that work to alleviate these challenges. As our intention is to describe how statistical methodology may work to identify disease variants for suicidality, we avoid the mathematical details of the methodologies presented.

Psychiatry deals with morbid psychological experience. This suggests that central to psychiatry's concern is the mind as opposed to the body. Yet, it is often the afflicted body rather than the mind that the patient presents to the clinician. In addiction, psychiatry classification has an underlying hierarchical bias for organic (somatic) disorders. Furthermore, many disorders such as generalised anxiety disorder and mood disorders have bodily manisfestations that are taken for granted in the consultation process or translated and relabelled as pointing towards psychological/emotional distress. This suggests that Cartesian mind-body dualism continues to significantly influence psychiatric concepts, classification and practice. In this presentation, the role of the body as model, metaphor, symbol, object and experiencing subject will be analysed with illustrative examples from clinical practice and literature. I will rely on Kafka's Letter to Father, Elfriede Jelinek's Piano Teacher, and Minkowsky's Lived Time.

The psy fields are predicated on the cartesian notion of a mind-body dualism.Suffering is understood to stem either from problems of mind or from problems ofphysiology. A related dualism is that of the “biological” and thatof “cultural”. Recent commentators have worked at great length tocollapse this dualism in day to day work with patients. At the same time, itclearly forms a fundamental part of medical epistemology. From a transculturalperspective, it is increasingly clear that there exists the possibility forconsiderable difference in the four “Es”: Experience, expression,explanation and expectations related to suffering. This variation is in largepart related to the epistemic structure underlying any given culture, and, takenas such, can present a considerable challenge to consultation-liason psychiatry.A patient may experience suffering that is expressed in the form of strangesensations in a specific parts of the body. This is then explained as aconsequence of a certain process that is culturally syntonic, and then expects acertain course of suffering as well as treatment. Given that we tend to take ourepistemic perspectives for granted as representative of the “world as itis”. The C-L psychiatrist who does not take these variations intoconsideration could all to easily arrive at a misdiagnosis and as sucherroeneous treatment.

Somatization concept should be considered in biopsychosocial integrity. Thispresentation reviews the social aspects of somatization. The description ofsomatization evolved in time in order to include the social aspects. Thedifferences of somatization between societies, somatization concept in westernand Eastern medical thought, modernist theory on the evolution of somatization,research which confirm and which do not confirm the modernist theory werereviewed. The pos-modern approach which constitutes a new paradigm in culturalpsychiatry, prefers to study the mental disorders through the culture, insteadof comparing them cross-culturally. In this context, first the culture-boundsomatization diagnosis of non-Western cultures, then the fashionable diagnosisof Western culture in which the somatization is hiding were reviewed.

ADHD is often associated with symptoms of emotional lability (EL), such as irritability, hot temper, low frustration tolerance, and sudden unpredictable shifts towards negative emotions such as anger, dysphoria and sadness. EL has been consistently noted in the changing definitions of the ADHD construct and its diagnosis and is currently considered an associated feature of the disorder. However, it is still unclear how EL and ADHD are interconnected. Thus, 1186 children with ADHD-combined type and 1827 siblings (aged 6-18 years) were assessed for symptoms of EL, ADHD, associated psychopathology and comorbid psychiatric disorders with a structured diagnostic interview as well as parent and teacher ratings of psychopathology. EL was associated with increased severity of ADHD core symptoms, particularly hyperactivity-impulsivity, and more symptoms of comorbid psychopathology, primarily symptoms of oppositional defiant disorder (ODD), but also affective symptoms, and substance abuse. However, EL was only partly explainable by the severity of ADHD core symptoms and associated psychopathology, and seems to be more closely related to oppositional symptoms. Severity of EL in probands increased severity of EL in siblings but not prevalence rates of ADHD or ODD.

The dimensions of ADHD symptoms in adults have been discussed controversially. Beside the classical symptom domains as unattention, hyperactivity, and impulsivity, other symptom clusters as emotional dysregulation are in debate. The aim of this presentation is to update the recent discussions on this topic by reviewing current positions and empirical data as well as presenting own data. The relationship between the scales with emotional contents in the Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS) compared to other established ADHD rating scales was explored in a sample of 600 ADHD patients. The aim is to clarify whether the symptoms are independent of other ADHD domains.

ADHD in adults is frequently associated with unstable or irritable moods reflecting difficulties with emotion regulation. Effect sizes of drug treatments on symptoms that reflect difficulties with emotion regulation, are similar to those on core ADHD symptoms, with co-variation of around 0.8 between the two types of symptoms during the treatment response. We therefore set out to investigate whether variability in mood results from the same aetiological processes that lead to variability in behaviour and cognitive performance in ADHD. Using real-time self-monitoring of emotional states and ADHD symptoms every two hours for 3-5 days, we characterised the mood changes in ADHD. Variability in both mood and ADHD symptoms (measured as the standard deviation) were significantly correlated with self-rated ADHD symptoms of inattention and hyperactivity. Subsequent analyses will link the observed symptom changes to cognitive-electrophysiological measures which are reliable indicators of core processes that underlie cognitive deficits associated with ADHD. We previously showed that a familial reaction time (mean and variability) factor explains 70% and commission and omission errors 20%, of the familial effects on ADHD. This finding concurs with the developmental model of Halperin which postulates that ADHD is linked to an early-appearing and enduring subcortical dysfunction, reflected in reaction time variability, while persistence/desistence of ADHD is dependent on maturational changes in executive control during adolescence reflected in commission and omission errors. We propose that at a behavioural level the subcortical deficit leads to dysregulation of a number of processes, including attentional, impulsive and emotional control.

The core psychopathology of ADHD comprises attentional deficits, hyperactivity and impulsivity. At least in subpopulations the majority of individuals suffering from ADHD present with emotional symptoms additonally. There is an ongoing and controversial debatte whether emotional symptoms belong to the disorder as further intrinsic ADHD psychopathology or may have their origin in comorbid affective disorders. There is growing evidence that emotional symptoms of ADHD as measured by the Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS) respond to treatment with Methylphenidate (MPH), while the classical symptoms of depression or anxiety disorder show no significant improvement.

We report on a 24-week, placebo controlled treatment study with MPH-extended release in 359 adults with ADHD. Emotional symptoms were assessed with the WRAADDS. Symptoms of depression and anxiety were endorsed by use of the Symptom Checklist-90-Revised (SCL-90-R).

As compared with placebo we found a significant treatment response in favour of MPH-ER regarding emotional symptoms like affective lability, emotional overreactivity and temper control. The psychopathology of depression and anxiety did not display a significant treatment response.

There is strong evidence for a heritability of major depression as shown by family, twin- and adoption studies. Several studies suggest a heritability for unipolar depression between 35 and 75% which is much lower than the heritability of bipolar disorder or schizophrenia. There is no doubt, that major depression is not caused by any single gene but it is a disease with complex genetic features. Furthermore, some subtypes, as early-onset or recurrent depression may have a higher heritability than other forms of depression. Neuroticism as an intermediate phenotype of MDD, which is a trait that reflects a tendency toward negative mood states, and has been linked to internalizing depressive conditions. For these reasons Dan Rujescu will present genome-wide and candidate gene studies, demonstrating a genetic approach for discovering potentially important pathogenic pathways for which clinically powerful (bio)markers may eventually be developed. He will discuss neuroticism as an intermediate phenotype of MDD, which is a trait that reflects a tendency toward negative mood states and has been linked to internalizing depressive conditions.

cAMP-specific PDE4 are a family of enzymes capable of hydrolyzing cAMP to 5’AMP. cAMP plays a major role in synaptic plasticity, neurite outgrowth, and neuronal differentiation and survival and recent studies demonstrate involvement of cAMP in pathophysiology of depression. The cAMP-specific PDE4 can be differentiated from other PDE families by sequence identity in the catalytic region of the protein and by their ability to be inhibited by a specific class of drugs, of which rolipram is the prototype. PDE4 enzymes are also unique in having ‘signature’ regions of sequence, called upstream conserved regions (UCR1 and UCR2), located in the N-terminal region of the proteins. There are four PDE4 subfamilies, encoded by separate genes (PDE4A, PDE4B, PDE4C, PDE4D), all are expressed in brain. A few studies suggest that PDE inhibitors show antidepressant-like effects in rodents. To examine the role of PDE4 in depression, we characterized various isoforms of PDE4 in human brain. Expression of PDE4A1, PDE4A4, PDE4A10, PDE4B1, PDE4B2, PDE4B3, PDE4D3, PDE4D4, PDE4D5 and PDE4D9 variants were characterized. All, except PDE4A10, PDE4B1, PDE4D4 or PDE4D5 variants, were highly expressed in human brain. When compared, we found that expression levels of PDE4A1, DE4B2, and PDE4A4 were decreased in PFC and hippocampus of depressed subjects, whereas, no change was observed in expression of PDEB3, PDE4D9, and PDED3 variants. Our study for the first time provides evidence of variant specific alterations in PDE4 in brain of depressed subjects and indicates that these variants may be used as site-specific therapeutic target(s) to develop novel antidepressants.

The aim of the “Therapy Evaluation Project” was to examine the therapy outcomes of all violent and sex offenders treated by the Zurich Criminal Justice System between January 1997 and the 31st of December 2005.

This included all the court-ordered therapies at the prisons of the Canton of Zurich as well as outpatient treatments that were carried out after release from detention (or instead of detention). The final treatment sample consisted of N=222 treated violent and sex-offenders. A representative sample of untreated violent and sex-offenders served as a control group.

After a mean time at risk of six years, the recidivism rates of the offenders were reviewed. Two types of recidivism were defined:

1. (1) The listing of a new conviction in the criminal record or

2. (2) offense relevant behaviour documented by the therapists, the probation services and/or other authorities.

The recidivism rate for treated violent and sex-offender was 12% compared to 20% for the untreated controls. By juxtaposing the various criteria/definitions of recidivism, the standards for evaluating the effectiveness of therapy will be debated.