Catatonia is an intriguing psychopathological dimension and the discussion about the clinical relevance of catatonic symptoms in psychiatry is continuing for at least 125 years. The debate started from the original description by Kahlbaum and was further elaborated by Kraepelin and Bleuler who incorporated catatonia in their broad concept of schizophrenia. They regarded catatonic symptoms merely as an integral part of schizophrenia. In addition, periodic catatonia was described by Leonhard that has a considerable hereditary loading, shows a phasic course with alternating hyperkinesia and akinesia and can be delineated from the akinetic-hyperkinetic motility psychosis which belongs to the cycloid psychoses.

Over the past decades, the prevalence of the diagnosis of catatonia as a separate disease and as subtype of schizophrenia is decreased considerable. This phenomenon is most probably the result of changes in the diagnostic criteria as well as underrecognition of this symptom dimension.

Today's research is focussing on the pathophysiology, genetics and treatment of catatonia. As demonstrated in factor analytical studies, this disorder can be considered as a separate psychopathological dimension. Apart from the endogenous catatonias belonging to either the periodic catatonia or catatonic schizophrenia, the catatonic dimension is present in about ten percent of newly admitted patients with affective or schizophrenic psychoses.

In for different presentations, the need for a differential diagnosis of catatonias will be outlined as well as their genetic and pathophysiological backgrounds and appropriate treatment strategies, such as electroconvulsive therapy.

Originally considered by Kahlbaum to be an independent disease entity characterized by mental and motor abnormalities, catatonia was later viewed as a subtype of schizophrenia as it is the case in current classifications like ICD-10 and DSM-IV. Since catatonic symptoms were observable not only in schizophrenic psychoses, but also in affective, somatic or even psychogenic disorders, many researchers today consider catatonia as a nosologically unspecific syndrome. In the end, the traditional conceptions did not succeed in defining catatonia as a clinically homogeneous and valid diagnosis.

An independent conception of catatonia was elaborated by the Wernicke-Kleist-Leonhard school of psychiatry. Based on a precise differentiation of diagnostically specific qualitative psychomotor disturbances, two essentially distinct forms of catatonic psychoses have been separated which differ in symptomatology, prognosis and treatment: on the one hand periodic catatonia, and on the other hand the group of systematic catatonias.

Periodic catatonia usually has an acute onset, shows a bipolar and polymorphous symptomatology and runs an intermittent course. After one or more acute attacks, adynamic residual states of varying degrees of severity develop. Hyperkinetic and akinetic distortions of psychomotor activity are characteristically intermingled in attacks and residual states.

In contrast, systematic catatonias begin insidiously, run a chronically progredient course without remissions and develop clear-cut and stable residual states. Six subtypes can be distinguished, each of which is characterized by a specific symptom constellation.

Catatonia has attracted increasing attention in relation to basic theoretical problems of psychiatry. Periodic catatonia (MIM 605419) is characterized by qualitative hyperkinetic and akinetic psychomotor disturbances through psychotic episodes, and debilitating symptoms in the long term with psychomotor weakness, grimacing facial movements, and apathy. Our aim was to identify new association loci for periodic catatonia a subphenotype of schizophrenic psychoses. We therefore performed a genome-wide association analysis using SNP Microarray and DNA pooling (SNP-MaP) with 500K Affymetrix arrays. We pooled DNA of 245 cases in three biological replicates (n=84, 84, 77) and 216 controls in two biological replicates (n=108, 108). All pools were processed in three technical replicates. Array data was analysed with a modified version of GenePool. We determined the mean relative allele signal value (RAS) of the technical replicates of each pool and compared each case pool with the combined controls. We used a 5-SNP sliding window approach and defined clusters as potentially associated loci if they overlapped in all biological replicates. We then verified pooling data at single genotype level for associated array SNPs at five selected loci using TaqMan assays in an extended cohort (344 cases, 585 controls). Two of these loci showed significant association at single marker (p=0.0002) and haplotype levels (p=0.0042), even after permutation correction (pc=0.0007; pc=0.0224). Our data show that hybridization intensities of pooled DNA correlate well with individual genotyping results. Thus DNA pooling is a useful strategy for GWAS since we were able to detect significant association loci in a complex disease.

The history of electrophysiological methods in Psychiatry is studded with ups and downs. Recently, several factors contributed to the renascence of the electrophysiological methods in schizophrenia research; in particular: a) the validation of previously reported electrophysiological findings by means of functional brain imaging techniques; b) the possibility offered by electrophysiological techniques to study brain's systems physiological and pathological activity with a high temporal resolution; c) a different conceptualizations of psychopathological phenomena, no longer considered as the result of a dysfunction of one or more brain regions, but as a consequence of the failure to integrate the activity of different areas. Main deliveries of such renascence include: advances in the study of abnormal functional connectivity underlying schizophrenia symptoms and the identification of electrophysiological endophenotypes. Notwithstanding the fact that electrophysiological abnormalities were shown to be related to diagnostic subtypes, risk factors, symptom dimensions and prognosis, electrophysiological methods are still of limited impact in clinical settings, and their application is confined to the exclusion of “organic” brain pathology.

Depression is a frequent co-morbid condition in diabetic patients. In controlled studies 9% fulfilled criteria for major depression and 26% reported elevated depressive symptoms. Depression rates are twofold higher in diabetic patients than in the non-diabetic population (major depression 5%; elevated depressive symptoms 14%). Diabetes specific risk factors like occurrence of complications, poor glycaemic control, insulin therapy in type 2 diabetic patients are statically associated with elevated depression rates. Furthermore the presence of depressive symptoms in non-diabetic subjects is associated with a significant higher diabetes risk in the future.

Depression in diabetic patients is linked with poorer diabetes self care behaviour like adherence to medication, keeping a healthy diet and physical exercise. The co-morbidity of diabetes and depression has also a negative impact on quality of life, which is greater than the comorbidty of depression and other chronic somatic diseases. Longitudinal studies indicate that depression in diabetes is related to a poorer prognosis. The risk for the development of complications is significantly higher in depressed than in non-depressed diabetic patients. Representative studies showed a significantly higher mortality in diabetic patients with depression than in non-depressed diabetic patients (hazard ratios between 1.67 to 2.6). The results also suggest that these negative consequences of depression are not only present in diabetic patients with severe forms of depression but also in patients with rather mild depression. In summary epidemiological findings imply that depression in diabetes is an important clinical condition warranting clinical attention as well as scientific interest.

The mechanism or pathogenesis that underlies the strong association between depression and diabetes is poorly understood but there are tentative models to explain the co-morbidity. The conventional model, namely that the psychological burden of living with diabetes leads to higher rates of depression, is not fully supported by the current evidence. Additional models include

1. a) the possibility of shared developmental origins between diabetes and depression

2. b) the direct effects of hyperglycaemia, hypoglycaemia and related metabolic dysfunction on the brain and

3. c) common mediators such as chronic stress response leading to pro-inflammation.

The potential for research into the above postulated pathways is vast and may lead to identification of new modifiable targets for intervention.

In this lecture, an overview will be given of the literature concerning treatment for comorbid diabetes and depression. A systematic review and analysis will be presented. It turns out that, although many clinicians and researchers find this an important subject of research, and although the clinical implications of such research seem obvious, randomized clinical trials evaluating effectiveness of treatment are scarce and often the numbers of patients included are small. However, all RCTs point in the direction of efficacy of treatment of this combined condition in terms of combined impact. Severity of depressive symptoms and glycemic control are most often used as outcome measures. Psychotherapeutic interventions show a moderate to large effect on both ; antidepressant treatment as well as collaborative care show moderate effects on depressive symptom severity. The clinical, public health and research implications of these findings will be discussed.

Diabetes and depression on their own are debilitating and costly diseases. Their co-existance presents further treatment and funding challenges. This session will provide an overview of the economic dimensions of this comorbid relationship and present the findings of a systematic review of evidence related to this. The review found a growing literature demonstrating: increased resource use and health care costs, unemployment and lost productivity; poorer quality of life; and a higher risk of mortality arising from the co-existance of these illnesses. While there are some good quality studies evaluating the efficacy/effectiveness of various treatments, few include an economic evaluation and the generalisability of those is unclear. Therefore, while the evidence suggests little doubt of the broad-ranging economic impacts on patients, health care systems and wider society, there is still a gap regarding the cost-effectiveness of alternative approaches to the treatment and long-term management of this comorbidity within the context of limited health care budgets.

Subclinical depression is a condition in which a person has clinically relevant depressive symptoms, but does not meet criteria for a depressive disorder. In this presentation, the different operationalizations of subthreshold depression will be presented, and we will focus on the importance from a clinical point of view, as well as from a public health public point of view. Subthreshold depression has important consequences for the quality of life, but not as much as major depression. It also results in huge economic costs on the individual level, but again less than the costs associated with major depression. Because subthreshold depression is more prevalent, the total costs of subthreshold depression on the population level are, however, comparable to those of major depression. It is also clear that subjects with subthreshold depression have an increased risk of developing a major depression. How large that chance is depends on several factors, including the definition of subthreshold depression. Finally, the results of a meta-analysis will be presented in which the effects of psychological treatments of subthreshold depression are examined. This meta-analysis shows that psychological treatments can be treated effectively, and there is a trend indicating that these interventions can prevent the onset of major depression.

In the last two decades enormous progress has been made in the characterization of premature ejaculation (PE). Although lifelong (primary) PE and acquired (secondary) PE has been known since the 1980s, a new classification of PE has been proposed in 2006 by Waldinger et al., who distinguished two other PE subtypes, e.g., premature-like ejaculatory disfunction and natural variable PE. In 1943, Bernhard Schapiro noted that family members of men with PE often have PE as well. In 1998, Waldinger et al postulated that lifelong PE, and particularly the short intravaginal ejaculation latency time (IELT), may be genetically determined. They postulated that the IELT is distributed according to a continuum, from men who always ejaculate very rapidly to men who always ejaculate after a very long intravaginal ejaculation time. Research in male rats showed this continuum. In two stopwatch studies, such a continuum was also shown in a random sample of men. In 2009, Janssen et al. publish ed a DNA study performed in men with lifelong PE. This study showed that 5-HTT polymorphism was involved in the ejaculation latency time. It appeared that in men with lifelong PE, males with LL genotype had a 100% faster ejaculation time than men with an SS genotype. It is postulated that the IELT is genetically determined by a cluster of genetic polymorphisms of the 5-HTT, 5-HT receptors, 5-HT enzymes and/or polymorphisms of other neurotransmitter systems.

Studies in humans and animals have suggested that the central dopaminergic system is involved in all components of male and female sexual behavior: desire, erection, orgasm and satisfaction. Copulating activity enhances DA release in the nucleus accumbens as measured by microdialysis in male rats. This rise in DA release lasts until ejaculation and then declines during the refractory period.

Dopaminergic agonists such as L-dopa, apomorphine, amantadine, bupropion, amphetamines and cocaine have been reported to arouse sexual behavior. Short term use of cocaine and other drugs that increase dopaminergic activity (Marijuana, MDMA) facilitate sexual desire and erection and delay ejaculation. These effects are reversed in chronic abuse when brain DA is depleted.

Central dopaminergic blockers, like first generation antipsychotics suppress sexual functioning via the D2 receptors blockade and the corresponding elevation in plasma prolactin levels. Due to their weak antagonistic activity at D2 receptors, second generation antipsychotics are associated with fewer sexual side effects and thus provide an option in the treatment of patients with schizophrenia.

Enhancement of dopaminergic activity by the addition of the DA agonists or bupropion, a norepinephrine-dopamine reuptake inhibitor, has been reported as an effective approach in the management of antidepressant-induced sexual dysfunction. The significant facilitating role of the DA system on sexual function should not be viewed independently. The dopaminergic system interacts with other systems like gonadal hormones, Nitric Oxide and serotonine in the complex neurobiology of sexual function.

The research of neurobiology and treatment of various disorders requires certain degree of homogeneity of the studied entities. In an ideal word, common etiology and/or pathogenesis would help to define homogenous entities. As our understanding of etiology and/or pathogenesis of mental disorders and diseases is lacking, we rely on various diagnostic systems to help us reach some degree of homogeneity.

The diagnostic criteria of sexual dysfunction(s) in the DSM-IV are rather vague and imprecise. Interestingly, we are not even clear when a sexual problem becomes a sexual dysfunction. As the new versions of the diagnostic systems (e.g., DSM-V) are being prepared, the classification and definitions of sexual disorders/dysfunctions are being considered.

The general classification issues that need to be and are addressed are specific duration of sexual dysfunctions, use of distress s a diagnostic criterion and quantification of severity and frequency. Strengthening and clarifying these three classification issues would probably help in defining more homogenous entities.

The broader yet more specific issues to be considered are inclusions of new diagnostic entities (persistent genital arousal disorder in women; adjustment disorder with disturbed sexual functioning; coercive paraphilic disorder), possible removal or reclassification of some sexual dysfunctions (e.g., sexual aversion disorder - remove or reclassify as specific phobia); collapsing some entities into one (dyspareunia and vaginismus into genitor-pelvic pain/penetration disorder) changing the names of some dysfunctions (premature ejaculation to rapid ejaculation); and redefining some dysfunctions (e.g. sexual desire and subjective sexual arousal in women).

Reigning theories about how the brain governs sexual behavior are the product of experimental investigations and observations in rodents. However, there is a growing appreciation of the fact that these animal models can not account for the sheer complexity of human sexuality. The need for human studies coincides with the exponential growth of the use of medical scanners for the purpose of visualizing human brain activity in vivo. Over the last decade, some 50 of these brain imaging - or neuroimaging - studies have appeared in the field of sexuality research.

In this lecture I will give an overview of the contribution neuroimaging has made to knowledge about the sexual brain. These studies cover a large area of human sexuality, including sexual orientation and preference, sexual desire and arousal, genital stimulation and orgasm, as well as sexual dysfunction and paraphilic disorders. Significant progress, relative to animal studies, has been made in understanding the role of the cerebral cortex, the prefrontal cortex in particular. At the end of the lecture, I will touch upon possible future research directions in the field of human neurosexology.

There is a high prevalence of panic disorder (PD) in the community. The National Comorbidity Survey, a US study of over 8000 adults in the general population, found a lifetime prevalence rate of 3.5%. This is a higher prevalence than that reported in earlier epidemiological studies, which documented lifetime prevalence rates of between 1.2 and 2.4%. Panic disorder is typically a disorder of young adults, with an impact on quality of life, in terms of social, personal, and economic consequences, at least comparable to that of major depression. Benzodiazepines, as well as selective serotonine reuptake inhibitors (SSRIs) have been studied thoroughly in acute and long-term PD. However, there is a lack of data to answer the question if there is an enhanced efficacy with the combination of psychological treatments as well as to guide the clinicians what to do after non-response.

Generalized anxiety disorder (GAD) is a chronic illness with an estimated one year prevalence of approximately 3%, and a lifetime prevalence of approximately 6%. GAD (without depression comorbidity) is associated with significant impairment in quality of life and functioning which has been found to be comparable to major depressive disorder, and chronic medical illnesses such as diabetes and arthritis. At least 5 classes of drugs are available for the pharmacologic management of GAD (Bandelow et al., 2008), each acting via different mechanisms: (1) benzodiazepines (diazepam, lorazepam, alprazolam, etc) which augment inhibitory GABAergic activity; (2) monoaminergic reuptake inhibitors, consisting of SSRI drugs with serotonin selectivity (paroxetine, escitalopram, sertraline), SNRI drugs with dual serotonin/ norepinephrine activity (venlafaxine-XR, duloxetine), as well as some first generation tricyclics (imipramine); (3) azapirones (buspirone) which modulate monoaminergic transmission; and (4) pregabalin, which acts presynaptically to inhibit excitatory neurotransmission. Two other classes of medication (antihistamines such as hydroxyzine; antipsychotics such as quetiapine) and recently a herbal remedy, silexan, have also demonstrated efficacy in the treatment of GAD. Cross-study comparisons suggest that each class of drug has a different benefit-risk profile. However, relatively few double-blind, placebo-controlled head-to-head trials have been published which provide direct comparisons of the efficacy and safety profiles of drugs in each class.

Based on the sound knowledge of clinical psychiatry neuroscientists embark since over 20 years to discover the biological bases of mental disorders. Whereas the “window to the brain” was firstly dominated by neuroendocrine and biochemical models, we now have the possibility to use sophisticated brain imaging techniques which span from electrophysiology to techniques derived from nuclear medicine. Furthermore, the combination of brain imaging techniques with genetic variables promises to have a close insight into brain-environment interactions. For treatment of psychiatric diseases, multidimensional criteria for selection of a psychotropic medication is necessary to not only judge the clinical phenotype but also the functional phenotype and finally the genotype. Whereas the clinical phenotype is characterized by psychiatric syndromes including psychiatric and somatic comorbidity, the functional phenotype can be uncovered with neuroendocrine measurements, sleep physiology, imaging techniques as well as proteomics. Finally, the genotype can be characterized by single nucleotid polymorphisms (SNP), coupling as well as the determination of candidate genes. Imaging genetics is a new way to achieve insight in the genetic variables of changes on a cellular level which thereafter influence information processing and finally are represented in complex functional interaction of human behavior. Based on this knowledge it is evident that psychiatrists not only should be determined to the clinical symptomatology of their patients but also on the underlying biological processes which can in turn be influenced to various degress with pharmacological as well as non-pharmacological treatment modalities, since the brain has a specified way to get better.