Dopamine D2 receptor blockade is the main mode of antipsychotic action. The optimal occupancy of D2 receptors seems to be crucial to balancing efficacy and adverse effects such as extrapyramidal symptoms or hyperprolactinaemia. Partial D2 receptor agonism, different pre- and postsynaptic D2 receptor antagonism, serotonergic antagonism and modulation, and neurotrophic effects contribute to differentiated antipsychotic efficacy, less side effects, favourable effects on the negative and cognitive symptoms of schizophrenia, etc. In addition, neurotrophic effects of the 2nd generation antipsychotics increase neuronal plasticity and synaptic remodelling in the striatum, in the prefrontal cortex and hippocampus, which may normalise glutamatergic dysfunction and structural abnormalities postulated by the neurodevelopmental disconnection hypothesis of schizophrenia. We demonstrate these mechanisms using various antipsychotics and serotonin manipulations in animal models of schizophrenia (MK-801).

Schizophrenia is a complex disorder and the view that schizophrenia is caused by hyperdopaminergic activity is an oversimplification. In fact, there are clinical evidence in accordance with a hypodopaminergic condition. Thus, untreated patients show motor disturbances in line with a decreased dopamine activity in the extrapyramidal system, likewise cognitive deficits and negative symptoms.

In our research we have explored the evidence of schizophrenia as a hyper- or hypodopaminergic condition. With Positron Emission Tomography (PET) we have not seen any evidence of increased D2-dopamine receptors in the brain of never medicated patients. The major dopamine metabolite homovanillic acid (HVA) was lowered in CSF in line with a decreased dopamine turnover in the brain. Tyrosine is precursor to the synthesis of dopamine and for that aim we have made transport studies in an in vitro model with fibroblasts to determine tyrosine kinetics. The results demonstrated that tyrosine transport is lower in patients with schizophrenia in comparison to healthy controls. Tyrosine kinetics measured with PET demonstrated dysregulation of tyrosine transport into the brain.

We have found evidence of schizophrenia as a hypodopaminergic condition. This fact is a problem realizing that our antipsychotics are D2-dopamine antagonists, thus decreasing dopamine activity even further. The concept of schizophrenia as both a hypo- and hyperdopaminergic condition may explain why clozapine, a week D2-antagonist, works more efficiently than other antipsychotic compounds. It should be recognized that positive symptoms are, at least partly, related to changes in dopamine activity and therefore respond very efficiently to D2-dopamine antagonists.

The human-type consciousness (defined as ability of self-recognition) has high evolutionary advantage, but the complexity of its anatomical/neurochemical background makes it prone to disturbances. Schizophrenia is one of cognitive disorders, arising from deficits in neural connectivity and in neurotransmission. The neurochemical hypothesis points to the disturbances in dopaminergic transmission: hyperactivity in mesolimbic and striatal systems (responsible for positive symptoms) with concomitant hypofunction of mesocortical system (hypofrontality and negative symptoms). This poses difficulties for pharmacotherapy: dopaminergic receptor blockade abolishes positive, but may aggravate negative symptoms. Difference in serotonin control of various dopaminergic subsystems permits to overcome some difficulties. The neurodevelopmental hypothesis of schizophrenia underlies the role of prenatal and perinatal stress disturbing neuronal migration leading to disrupted cortical architecture. In neurodevelopmental disorders stress hormones are the wreckers and neurotrophins are protectants. A role for BDNF is suggested as its levels are decreased in schizophrenic brain and its Val66Met polymorphism is associated with earlier onset of the disease. The emergence of schizophrenia in late adolescence may be caused by inadequate BDNF supply at the time of final maturation of prefrontal cortex, and attempts of correction of BDNF level may be worth trying. It may be assumed that schizophrenia is the result of wrong interactions between stress, genetic and developmental factors. Studies on candidate genes for schizophrenia and of endophenotypes lead to better understanding of the disease and prospects for more efficient therapy. The question arises why the genes involved in schizophrenia had not been eliminated in the course of evolution?

From about 1910 till the mid 1950s, medical sexology has mainly been practiced by psychiatrists. Although many psychiatrists used a psychoanalytic approach, particularly the psychiatrists at the “ Institut fur Sexual Wissenschaft” in Berlin introduced a biological, e.g. endocrinological, approach to treat sexual dysfunctions. However, this famous Institute was destroyed by the Nazis in 1933 and this marked the end of a very fruitful biological period in medical sexology. After World War II, sexology became more and more investigated and practiced by psychologists who at the time claimed successes of a behavioristic approach. Gradually, psychiatrists lost their interest in sexology. Currently, and internationally, sexology is not any more an important part of psychiatry. Since the 1990s, but particularly after the introduction of Viagra in 1998, sexology has become a major part of urology. The current state of sexology being practiced mainly by psychologists and urologists may be harmful for a balanced development of medical sexology.

Progress in the field of sexual neuropsychopharmacology has shown that sexual functioning is related to brain functioning. This means that there is a new role for (neuro)psychiatry in sexual medicine. Psychiatrists, who more than psychologists and urologists are better equipped to deal with psychopharmacotherapy and psychotherapy, should take part in the new scientific developments, both with regard to drug treatment as in psychotherapy of sexual disorders.

The DSM diagnostic criteria of sexual dysfunctions have been widely used by clinicians, researchers and in pharmaceutical trials. However, these diagnostic criteria do not reflect the developments in the field of sexual medicine. These criteria are vague and do not include many of the criteria used in other mental disorders classified in the DSM. Better defined operational criteria are needed to define more homogenous population samples and to help answer some basic research questions.

Some of the issues that need to be addressed in the new revision of the sexual dysfunctions diagnostic criteria include the duration of sexual dysfunction, intensity and frequency of sexual dysfunction, the use of distress as a diagnostic criterion, whether there are specific differences in diagnosing female and male sexual dysfunction, validity of some diagnostic entities (e.g., sexual aversion disorder), reclassifying some sexual dysfunctions (e.g., dyspareunia as a pain disorder), and the overlap of diagnoses.

Further deliberation of sexual dysfunction classification should also include two core questions: a) when does a sexual problem become a sexual dysfunction, and related to that b) what do we consider “normal” and/or what is a biological variation of sexual functioning (e.g., are rapid ejaculation and extremely delayed ejaculation dysfunctions or normal variants of sexual performance at the very ends of the spectrum?).

This presentation will review in detail the deficiencies of the standing diagnostic criteria and will provide suggestions for improvement of these criteria based on evidence from the literature and on recommendations of expert panels.