This presentation will be introduced by the different disease conceptions between Europe and West African cultures.

The classical assumption of universality of neurological substrate will be discuss in confront with cultural relativist perspectives going back to nosology.

Some questions will be adress in the fields of compared subjectivity and phenomenology.

Some final remarks about the importance of Ethno-psychiatry will be done.

Since countries have relaxed immigration policies, mental health professionals have been confronted with clinical pictures necessitating a different reflection on their practice of psychiatry based on a western system of reference. Misdiagnosis can be the source of unnecessary hospitalization, harmful drug treatment and inadequate management of cases. From the perspective of migrating populations, they undergo a process of change with the necessity to cope with the host culture while preserving their previous cultural values. Sometimes migration awakens new hopes like the belief seen lately among Israeli Ethiopians that spirits won't migrate with them and won't anymore require their attention. It soon becomes apparent that the reality is different and Zar spirits pathology appear, provoking questions about its meaning. Beer-Yaacov Mental Health Center is located south of Tel-Aviv in an area where 20% of the Ethiopian community lives. Patients of Ethiopian origin, unresponsive to “traditional” Western treatment are referred to the hospital outpatient clinic for examination at the ethnopsychiatric consultation service. With the help of three clinical vignettes we will describe the psychopathology due to the issues of healers that can't heal or of people meant to be healers that couldn't fulfill their apprenticeship because of migration. We will show how an ethnopsychiatric-oriented interview combined with an ethnopsychiatric analysis of the clinical picture, allow a better diagnosis even in the context of a conventional institutional frame.

The research we are striving to foster in Italy, aims at identifying the nature of the spaces linking the well-known neurobiological paths of interpersonal experience and the less-known psychological and phenomenological paths of the intercultural relation. The challenge consists in understanding the experience of plurality and therefore how you can pass from a “relational” to a “multicultural” mind.

An approach, to be really multicultural, intercultural and transcultural, must be based on the dialogue between different disciplines. Therefore, if European psychiatrists will not be opened to cultural anthropologists, psychologists, sociologists, ethnologists, they will not progress and there will be the risk of closing themselves in a conclave detached from the interconnections of globalisation.

We hope that this first symposium between psychopathologists and cultural psychiatrists may prompt a debate between experts in the field of psychopathology and cultural anthropology to deconstruct Western culture seen as a repository of the “medical basic knowledge”.

Today, more than ever, it is increasingly important to consider not only the Western culture models (e.g. the neurobiological point of view) but also specific models of other cultures. The latter either disregard our medical background or they “do not let themselves be colonised”.

Those who work in the field of psychopathology are confronted to systems of thought different from the system of thought studied by Western psychopathologists. This makes to think that the right way to consider “psychopathology” is as a “cultural psychopathology”.

Gene-environment interactions (GEI) were recently found to contribute to the etiology of mood disorders and suicidal behavior in children adolescents and young adults. Childhood adversity may produce a biological and clinical diathesis for mood disorder and suicidality that endures into adulthood. Life events predict depression and suicidal ideation or a suicide attempt in children, adolescent and young adult carriers of the S allele of the 5-HTTLPR polymorphism. This finding was replicated in children, adolescents and young adults. We reported on a third functional allele in the serotonin transporter gene (A trialleleic polymorphism) that may give a new clue to the GEI in depression and suicide. Some new biological data supporting the validity of this interaction will be presented.

The antisaccade task is a model of the conflict between an unwanted reflexive response (which must be inhibited) and an appropriate volitional response (which must be generated). In this talk I will present a study of the neural correlates of these cognitive components separately using a delayed saccade paradigm to dissociate saccade inhibition from generation. Event-related functional magnetic resonance imaging (fMRI) was carried out in healthy human volunteers. It was found that the right supramarginal gyrus showed significantly greater activation during response inhibition compared to response generation, suggesting a role in saccade inhibition or stimulus detection. The right lateral frontal eye field and bilateral intraparietal sulcus showed evidence of selective involvement in antisaccade generation. Ventrolateral and dorsolateral prefrontal cortices showed comparable levels of activation in both phases of the task. These areas likely fulfil a more general supervisory role in the volitional control of eye movements, such as stimulus appraisal, task set, and decision making. The findings will be discussed in relation to data suggesting that antisaccade deficits constitute an endophenotype for schizophrenia and in relation to pharmacological studies of brain function during antisaccade eye movements.

Prepulse inhibition (PPI) refers to the attenuation of the amplitude of the startle reflex in response to sudden intense stimuli (pulse) if preceded by a weaker sensory stimulus (prepulse). PPI reflects sensorimotor gating i.e. the ability to filter out irrelevant information in the early stages of processing so that attention can be directed to more salient environmental features. Recent neuropsychological studies show greater PPI in healthy individuals with superior performance on tasks that rely on the integrity and efficiency of prefrontal cortical (PFC) function. The PFC is an important node in the cortico-striato-pallido-thalamic circuitry, which modulates PPI. PFC function has been examined in relation to the COMT Val158Met polymorphism, which determines basal PFC dopamine (DA) neurotransmission levels and consequently, performance on PFC DA-dependent cognitive tasks. Met/Met individuals have the best PFC performance or greater “efficiency” and the highest PPI, Val/Val the worst performance and the lowest PPI, and Val/Met intermediate performance and PPI. Consistent with the increasingly accepted model of an inverted U-shape relationship between PFC DA levels and PFC function, the COMT inhibitor tolcapone as well as attention-to-prepulse, increase PPI in Val/Val individuals, while Met/Met individuals are unaffected or get worse. These findings strongly suggest that inhibition at the early stage of information processing is modulated by the PFC DA activity in a “top-down” fashion and this may account for the normal inter-individual variability in PPI and in cognitive performance.

Schizophrenia patients exhibit impairments in prepulse inhibition (PPI) of the acoustic startle response (ASR). PPI is commonly used as an index of sensorimotor gating. Results of animal studies and some human data suggest that PPI deficits are in part genetically determined, such that PPI could be an endophenotypic indicator of risk for schizophrenia, Thus, PPI deficits should already be present prior to onset of psychosis. To test this assumption, we investigated PPI in individuals with prodromal symptoms of schizophrenia and patients with first-episode schizophrenia.

Startle reactivity, habituation, and PPI of ASR were assessed in 54 subjects with prodromal symptoms of schizophrenia (35 at an early prodromal stage, 19 at a late prodromal stage), 31 first episode schizophrenic patients (14 unmedicated, 17 medicated), and 28 healthy controls. Patients were also examined with the Positive and Negative Symptom Scale and the Global Assessment of Functioning Scale.

Prodromal subjects and unmedicated patients with first episode schizophrenia showed significant PPI deficits, whereas schizophrenic patients treated with risperidone had almost normal PPI. In contrast, startle reactivity decreased with severity of symptoms but was relatively unimpaired in the medicated patients. With respect to habituation, prodromal subjects and schizophrenic patients did not differ from healthy controls.

PPI disruption is present in subjects in a prodromal state likely to proceed to schizophrenia, supporting the hypothesis that PPI disruption is an endophenotype of schizophrenia. In contrast, startle reactivity and habituation deficits were not evident in the prodromal subjects, but only in unmedicated patients with diagnosis of schizophrenia.

A key feature of schizophrenia is the inability to screen out irrelevant sensory input. Prepulse inhibition (PPI) of the startle response, a cross-species measure of sensorimotor gating, provides a valuable opportunity to study this feature. Patients with schizophrenia, first-degree relatives of patients with schizophrenia, patients with schizotypal personality disorder and healthy individuals scoring high on psychometric measures of psychosis-proneness display reduced PPI. Animal models of disrupted PPI have proved valuable for the evaluation of existing and potential new treatments for schizophrenia. Animal studies have also shown that PPI is modulated by the cortico-striatal-pallido-thalamic circuitry involving the prefrontal cortex, thalamus, hippocampus, amygdala, nucleus accumbens, striatum, ventral pallidum, globus pallidus, and subpallidal efferents to the pedunculopontine nucleus. Recent neuroimaging data from our and other laboratories confirm the involvement of this circuitry in (a) normal PPI in healthy people, (b) deficient PPI in patients with schizophrenia and related conditions, and (c) the effects of pharmacological agents relevant to the treatment of schizophrenic illness.

Cognitive impairment is a core deficits in schizophrenia and in bipolar disorders. The cognitive dysfunctions are related to the abnormal brain activation in these illnesses. Working memory and executive dysfunctions associated with prefrontal cortex abnormalities in these illnesses are known as an neuropsychological marker of vulnerability to the diseases.

The most important methods used in assessment of abnormal brain activation are neuroimaging methods and neuropsychologial tests. Current data show high coincidence between the level of performance on cognitive tests and activation of the brain. The data obtained in patients with schizophrenia and bipolar disorder show the significant association between level of hypofrontality (decrease of blood flow and intensity of glucose metabolism) and the level of impairment of the performance of prefrontal tests.

The Cogtest Battery it the novel computerized neuropsychological battery used for cognitive screening in different mental and neurological diseases. This battery consisted with tests for evaluation different domains of cognition, such as frontal functions (working memory and executive functions), verbal abilities (connected mostly with left hemisphere activation), attention, psychomotor speed, spatial and motor performance, memory and learning (associated with temporal lobe activation). Based on gold standard paper and pencil tests. The computer version of the tests and touch screen make possible to examine patients with motor disabilities - such as patients with Parkinson's Disease. The specific data management system make possible to eliminate data with artifacts.

Selected tests from the system are used as a cognitive stimulation during neurophysilogical assessment (EEG, EMG, EOG) and during neuroimaging, especially with F-MRI.

Cognitive dysfunction such as impairment of memory, attention, spatial and verbal functions plays important role in etiopathogenesis and clinical picture in neurodegenerative disorders. There are related with structural and functional abnormalities of different region of the brain connected with these cognitive processes. Cognitive dysfunctions caused severe functional and social disabilities of the patients. The neuroimaging methods such as F-MRI, or PET scan are very useful in diagnosis of structural and functional changes in the brain in neurodegeneration diseases, e.g. Parkinson's or Alzheimer's diseases. Neuroimaging during cognitive stimulations show different brain activation in patients with schizophrenia or neurodegenerative disorders in comparison to healthy subjects. F-MRI show increase of prefrontal cortex activation during n-Back test performance in healthy controls, while in patients with schizophrenia and Alzheimer disease this effect was not noted. In schizophrenia patients after treatment with risperidone (but not with haloperidol) the normalization of activation in different brain area was observed.

F-MRI assessment during N-back test (0 - back and 1-back tasks), encoding and recognition, visual discrimination performed in 9 patients with Alzheimer's Disease (AD) and 9 healthy subjects show abnormal activation in patients with AD. Among 9 patients with AD 5 were treated with rivastigmine, 4 received placebo. Cognitive improvement was observed after 3 months of treatment with rivastigmine - the same time fMRI showed an increase in brain activity in regions involved in attentional processes. This indicate that neuroimaging methods during cognitive stimulation may be useful in cognitive assessment in CNS disorders and in assessment of drug effect on cognition.

Prefrontal functions impairment in schizophrenia and bipolar disorder are are markers of vulnerability to the diseases. Our previous data showed association between Wisconsin Card Sorting Test (WCST) performance in schizophrenia with the polymorphism of dopaminergic genes)COMT, DRD 1) and with polymorphism of Brain-derived neurotrophic factor (BDNF) in bipolar disorders. The Src-family tyrosine kinase Fyn plays important role in the interaction between BDNF and glutamatergic receptor NMDA in prefrontal cortex. The possible association between the polymorphisms of BDNF and Fyn genes and performance on WCST and N-back tests in healthy subjects were assessed in 200 healthy persons, genotyped for the two polymorphism of BDNF gene (C/T, Val66Met) and three polymorphisms of the Fyn gene (-93 A/G, IVS10+37T/C, Ex12+894T/G). In the whole group, the T/T genotype of C-270T BDNF polymorphism was associated with higher percentage of conceptual responses on WCST. Male subjects with C/T genotype obtained better results on percentage of correct reactions in N-back test. No significant differences between any of Fyn gene polymorphisms and WCST performance were found. Better results on percentage of correct reactions in N-back test were obtained by subjects with G/G genotype of 93A/G polymorphism and with G/G genotype of FYN T/G polymorphism. Female subjects having T/T polymorphism of T/C polymorphism performed better as to percentage of correct reactions in N-back test. The results obtained may suggest a contribution of BDNF and glutamatergic system genes to working memory efficiency in healthy subjects and bipolar disorder, while in schizophrenia with dopaminergic system genes.

Pathological obesity may be related with impairment of impulse control and cognitive disturbances. In this study the cognitive frontal functions in relation to the polymorphism of candidate genes in patients with pathological obesity were assessed. The prefrontal functions were evaluatedmusing Wisconsin Card Sorting Test. The polymorphisms of genes connected with serotoninergic and dopaminergic system : 5HT2A, 5HT2C, 5HTT, DAT1, and COMT, and also the polymorphism of BDNF - involved with modulation of nervous system development and neuroplasticity were assessed. Polymorphisms of the genes were detected by RFLP and VNTR PCR methods.

The 100 subjects with pathological obesity, BMI>40 operated with Mason method were enrolled. The results of WCST were compared with the results of healthy sex, age and education matched controls.

Subjects with pathological obesity show significant worse results on all domains of WCST, compared to controls. The frequencies of the polymorphisms in the obese group were: 5HT2A -1438A->G - A/A - 11%, A/G - 50%, G/G - 39%; DAT1 VNTR in 15th exon - short/short - 13%, short/long - 34%, long/long - 53%; BDNF Val66Met (G->A) - A/A - 3%, A/G - 24%, G/G - 73%. Interesting results were obtained in the case of 5HT2C: a known polymorphism (-759C->T) could not explain the banding pattern observed. It is possible that we have found a novel polymorphism that strongly correlates with obesity. The results obtained show significant prefrontal dysfunctions in patients with pathological obesity which may be related to the polymorphisms of serotonin and dopaminergic system genes and possible association of the obesity with the new polymorphism of 5HT2C gene.