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PubMed2002

[Genetic hypothesis of schizophrenia].

It is now well demonstrated from family, adoption or twin studies, that genetic factors are involved in schizophrenia. Yet, the nature of these factors remains unknown. The disappointing results of the classical linkage studies are explained by the complex non mendelian inheritance, involving several genes interacting with environmental and/or maturation processes, and the heterogeneity of the clinical expression. The identification of genes having an influence on schizophrenia requires thus new strategies including statistical analysis with no assumption on the inheritance mode (non parametric methods) and the dissection of the heterogeneous syndrome using endophenotypes and/or relevant clinical features. Beside the hypothesis of a dysfunctional neurotransmission in schizophrenia (i.e. dopaminergic), evidence suggests that genes involved in neurodevelopment could also be candidate. The observation of caryotypic anomalies could also lead to new candidate regions or genes.

Brain↗

PubMed2002

Error rate on the antisaccade task: heritability and developmental change in performance among preadolescent and late-adolescent female twin youth.

We examined heritability of error rate on the antisaccade task among female twin youths. This task appears to be sensitive to prefrontal functioning, providing a measure of individual differences in inhibitory control associated with genetic risk for schizophrenia. The sample consisted of 674 11-year-olds and 616 17-year-olds, comprising the two cohorts of female twins from the Minnesota Twin Family Study, a population-based investigation of substance abuse and related psychopathology. We used biometric model-fitting methods to determine the relative magnitude of genetic and environmental influences on performance. In both age cohorts, the best fitting model contained additive genes and nonshared environment. Despite substantial age-related differences in mean performance levels (effect size = .81), additive genes accounted for greater than half the variance in performance in both age cohorts. These results are consistent with the hypothesis that antisaccade error rate might serve as an endophenotype for behavior disorders reflecting frontal lobe dysfunction or problems with inhibitory control.

Adolescent↗

PubMed2003

Tryptophan depletion, serotonin, and depression: where do we stand?

Tryptophan depletion is a widely used paradigm to study serotonin system-related mechanisms in the pathophysiology and treatment of depression. There is convincing evidence that tryptophan depletion primarily and selectively affects serotonergic transmission. The behavioral data in healthy controls with and without genetic risk for depression, and in patient populations during the symptomatic phase of depression and when being remitted, suggest a trait abnormality of serotonin function in depression and that antidepressants may compensate for the underlying deficit. Tryptophan depletion may be a useful tool to create more integrative models for the pathophysiology of depression that take into account neurobiological systems beyond monoamines. More recent studies combining tryptophan depletion with genetic variables may provide an important approach for studying gene/environment interactions using candidate genes to define endophenotypes, which ultimately will improve currently used diagnostic categories and help to generate more advanced models to understand the neurobiology of depression. This may lead to the development of truly novel treatment approaches for depression.

Brain↗

PubMedDate not supplied

[P50 component of auditory evoked potentials in persons with schizophrenia and their first degree relatives].

UNLABELLED: A pair of auditory stimuli presented in a 0.5 second interval cause a reduction of the P50 auditory evoked potential (P50 AEP) amplitude after the second stimuli in the pair. In some, but not all studies, a clear deficit of such P50 AEP gating was observed in schizophrenic patients. It was present constantly irrespective of the clinical state. This deficit was also found in first degree relatives of schizophrenic patients. However the results of the studies, as well as their interpretation remain controversial. AIM: To differentiate between P50 AEP in groups of schizophrenic patients, their healthy first degree relatives, as well as those in the control group. METHOD: 50 schizophrenic patients (ICD-10 criteria (DCR)) in early clinical improvement phase, 26 healthy first degree relatives, as well sa 46 healthy individuals with no psychiatric illness in the self-report and family history. All those studied were stimulated with 120 pairs of auditory stimuli (clicks), each of duration 2 mseconds and a sound intensity of 73 dB, with a 500 msecond interval between the stimuli in a pair (S1 and S2) every 8 seconds. A high-end filter of 70 Hz and low-end filter of 10 Hz were applied. Bio potentials were recorded from the head apex, relatively to the mastoid process (A1 + A2). Eyeball-movement artefacts were registered from the Fp1-A1 and Fp2-A2 potentials. The registered bio potentials were evened on-line. RESULTS: Relative (i.e. evaluated in relation to the potential after S1) lowering of the P50 potential after S2 was the most significant in the healthy control group (75%), in the other groups usually there was an increase in the S2 potential--higher in the schizophrenic patient group (-45%) and lower in their first degree relatives (-11%). CONCLUSIONS: (1) Healthy individuals suppressed the neurophysiologic response to the second pair of auditory stimuli much more than the schizophrenic patients and their healthy families. (2) No difference was seen in the suppression of the response between the schizophrenic patients and their first degree relatives. The results are coherent with the idea of the dysfunction of the P50 gating having endophenotypic traits as far as schizophrenia goes.

Acoustic Stimulation↗

PubMed2004

[Neuroanatomy and neurophysiology in schizophrenia].

Advances in neuroimaging and neurophysiological techniques have enabled detailed investigations of the brain pathophysiology of schizophrenia. In this article, we first overviewed neuroanatomical and neurophysiological studies of the superior temporal gyrus and anterior cingulate cortex in patients with schizophrenia, using structural magnetic resonance imaging (s-MRI), MR spectroscopy (MRS), event-related potentials (ERPs) and magnetoencephalography (MEG). Next, we discussed several key points for future research in psychiatric neuroimaging, such as disease specificity, heterogeneity, utility as endophenotype markers, relationship to psychosocial outcome, and application to clinical purposes. Finally, we described important issues, in terms of the infrastructure and system, which need to be improved in clinical psychiatry research in Japan.

Brain↗

PubMedDate not supplied

[P50 sensory gating disorders of auditory evoked potentials (AEP) in persons with schizophrenia].

The paper presents a review of recent data on research and clinical significance of gating of the P50 component of the auditory evoked potentials (AEP). Information filters are a necessary element for the proper functioning of the brain. It appears as though they have an important role in the information-transfer mechanisms. Neurophysiologically, they appear hypothetically in the sensory gating of the P50 component of the AEP. Schizophrenic patients and their first degree relatives do not have proper sensory gating of the P50 AEP. This suggests that there is a common biological base for these disorders. Some clinical aspects of the schizophrenic psychoses can be linked to this disordered gating. There are also notes which show the contrary. Currently we do not know whether the improper sensory gating of the P50 AEP is a trait endophenotypically linked to schizophrenia, or only something that partially explains the pathophysiology of the illness--especially since the described phenomena may be evoked in healthy persons.

Auditory Pathways↗

PubMedDate not supplied

[Working memory dysfunction in patients suffering from schizophrenia and their first-degree relatives].

UNLABELLED: Working memory deficits are considered to play an important role affecting not only the pathogenesis but also the course of schizophrenia. Numerous studies of schizophrenic patients and their first-degree relatives suggest that this impairment may be an indicator of susceptibility to developing schizophrenia. AIM: A comparison of selected working memory indicators in patients with schizophrenia, their first-degree relatives, and healthy controls. METHOD: Participants in the study were 99 patients with the diagnosis of schizophrenia (according to the ICD- 10-DCR criteria) in an early period of remission, their healthy first-degree relatives (N = 42), relatives with a history of psychiatric disorder (N = 14), and a control group of participants (N = 54) unrelated to the subjects and with no psychiatric history. Selected tests from the computer-aided Vienna Test Battery were used, measuring: reaction time (RT) in a task that required choosing among complex stimuli of two modalities, a tendency to perseveration (PERSEV), and immediate visuospatial memory span (CORSI). RESULTS: Schizophrenic patients' performance was found to be significantly inferior to that of controls on all the cognitive tests related to working memory: they had a longer reaction time in forced choice tasks, elevated perseverative tendencies and reduced immediate visuospatial memory span. Moreover, healthy relatives of schizophrenic patients performed significantly poorer than did the controls both as regards perseverative tendencies and visuospatial memory scan. Schizophrenic patients did not differ significantly from their close relatives in the degree of visuospatial memory span impairment. CONCLUSIONS: The findings indicate that working memory deficits as assessed by the tests used in the study may be related to familial susceptibility to schizophrenia. Therefore, the dysfunction may be taken into account in the capacity of endophenotype of such susceptibility.

Adult↗

PubMed2005

[Pathogenesis of bipolar disorders: genetic vulnerability and environmental factors].

It is now well-established that there is a genetic vulnerability for developing bipolar disorders. For instance, the rate of bipolar disorders in first degree relatives of bipolar probands (19%) is higher than in the general population (1%); monozygote twins have higher concordance rates for bipolar diseases (67%) than dizygote (19%); finally affective disorders are more frequent in biological parents than in adoptive parents in adopted bipolar patients. However, currently genes predisposing for the disease are not known, in part because bipolar disorders are very heterogeneous. New research strategies should be developed based on more homogeneous groups of patients defined by the presence of "candidate symptoms" or by the evidence of endophenotypes in healthy relatives. However, it is clear now that there is an interaction between the genetic vulnerability and environmental factors in the aetiology and course of the disorder. Environmental factors have been neglected for a long time because bipolar disorder was considered an endogenous disease. Thus, very recently, studies have shown that early trauma could contribute to the occurrence or the severity of the disease. During a lifetime, many environmental components (stressful life events, changes in daily schedules, drug abuse, some medications) could also trigger the onset of the pathology or the occurrence of new episodes. It is very important to recognize these factors in order to develop preventive strategies for limiting their impact.

Bipolar Disorder↗

PubMed2005

[Cognitive dysfunction and electroencephalogram in schizophrenia].

Recent developments in neuroscience, especially in neuropsychology and neuroimaging, have shed light on cognitive dysfunction in schizophrenia. Cognitive dysfunction may be the underlying basis of schizophrenic symptoms and also the vulnerability marker such as an endophenotype used in genetic studies. Among various cognitive functions, attention is currently focused on "social cognition" as a new realm of research which it may determine the social and occupational abilities of patients with schizophrenia. Recent studies indicate that the second-generation antipsychotics may improve some aspects of cognitive dysfunction in schizophrenia. This urges us to reveal whether such drugs also improve the long-term prognosis as well as quality of life of the patients. Although cognitive function has usually been evaluated by neuropsychological tests, it is advisable to employ electroencephalogram especially event-related potential, which has high time resolution, in combination with neuroimaging with high spatial resolution. In this paper, studies with event-related potentials including P50, MMN, Nd, NA, P300, and N400 are reviewed and we propose a pathophysiological model of schizophrenia from the viewpoint of information processing. The model consists of a controlled processing system (e. g., perceptual organization, and semantic integration) and regulatory system which is mainly automatic processing and enables the controlled processing to be efficient. We postulate that both systems will be primarily affected in schizophrenia and that disruptions in the regulatory system from any cause will impose. further burden on the controlled system and lead to psychosis. Finally, comprehensive and sophisticated assessment of these systems will be required in schizophrenia research.

Antipsychotic Agents↗

PubMedDate not supplied

[Eye movement disturbances and working memory deficit in bipolar affective disorder].

UNLABELLED: THE AIM AND METHODS: The aim of this study was to assess the intensity and frequency of eye movement abnormalities measured with infrared reflectometry, and working memory disturbances assessed with the Wisconsin Card Sorting Test (WCST). The study was performed in 87 patients with bipolar affective illness, in 119 patients with schizophrenia and in 90 healthy persons. In patients, the assessment was done during a mild symptomatic period or in remission. RESULTS: In patients with bipolar affective illness significant disturbances of eye movement and working memory compared with healthy subjects were found. Frequency and intensity of fixation abnormalities was less intense compared to schizophrenic patients, while smooth pursuit abnormalities had a similar degree. Working memory disturbances in bipolar patients were, as to the ability of formulation of logical conception, of similar degree as in schizophrenia. On the other hand, as to the effectiveness of thinking, no difference compared with healthy controls was found. CONCLUSIONS: The results obtained suggest that eye movement and working memory disturbances may constitute neurophysiological and neuropsychological endophenotypic markers of bipolar affective illness what makes possible using them in molecular genetic studies of this illness.

Adult↗

PubMed2005

Dissecting the suicide phenotype: the role of impulsive-aggressive behaviours.

Suicide ranks among the main causes of death in most Western countries and is, thus, an important public health problem. Over the last few years, it has been increasingly recognized that people who attempt or commit suicide have a certain individual predisposition, partly resulting from certain personality traits, in particular, impulsive-aggressive behaviors. The evidence suggests that impulsive-aggressive traits are part of a developmental cascade that increases suicide risk among a subset of suicides. These personality traits may also mediate familial transmission of suicidal behavior, defining a behavioral endophenotype that could be useful in molecular genetic studies of suicide. On the other hand, not all suicides are associated with impulsive-aggressive behaviors. There is a need to better understand the mechanisms mediating suicide among individuals with no history of impulsive-aggressive behaviors.

Aggression↗

PubMed2006

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: structural MR imaging changes and apolipoprotein E genotype.

BACKGROUND AND PURPOSE: Apolipoprotein E (apoE) genotype plays an important role in the development, maintenance, and response to injury of the central nervous system. It has been suggested that apoE epsilon4 genotype is a risk factor for several neurologic disorders. We investigated the correlation between the apoE genotype and radiologic data in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). METHODS: T1-weighted, dual fast spin-echo, T2*-weighted gradient echo, and fluid-attenuated inversion recovery MR imaging scans were obtained from 36 CADASIL patients (21-59 years of age). The number of lacunar infarcts and microbleeds and the presence of subcortical lacunar lesions were determined. The amount of white matter hyperintensities was assessed by using semiautomated segmentation software. The relation between the radiologic endophenotype of CADASIL and the apoE genotype was assessed by using a Student t test for unpaired data and Fisher exact test. RESULTS: White matter hyperintensities, lacunar infarcts, microbleeds, and subcortical lacunar lesions were not found to be associated with the presence of an epsilon4 allele. CONCLUSION: The variability of structural MR imaging lesions in CADASIL is independent of apoE genotype and other processes must underlie the variable natural history of the disease.

Adult↗

PubMed2006

[Eye movement in patients with schizophrenia].

To clarify the cognitive function of schizophrenia, the exploratory eye movement was investigated using S-shaped figures in patients with schizophrenia and their relatives. As a result, the exploratory eye movement has been found to be a biological marker that reflects a specific and trait factor of schizophrenia. Using the exploratory eye movement combined with brain functional imaging, the pathology of schizophrenia that the neural network centering on thalamus was damaged is being clarified. Moreover, the disease gene of schizophrenia may be discovered especially on the chromosome 22 using the exploratory eye movement as an endophenotype. In addition, the exploratory eye movement can be given as a powerful candidate of diagnostic tool for schizophrenia.

Adult↗

PubMed2006

[Hippocampus, structure of the brain and schizophrenia].

Schizophrenia is a clinically heterogeneous state without clearly defined pathogenesis. This limits the classification approaches with consequent lack of ability for individual treatment strategies. It becomes evident that hippocampus is a key structure in the neuropathology of schizophrenia and a concept of hippocampal reduction as an endophenotype of schizophrenia was established. The biggest support came from MRI volumetric studies. Despite that, due to some inconsistent findings, clinical consequences of hippocampal shrinkage are not yet clear. Contemporary methods of brain imaging (computation morphometry, voxel-based morphometry) could help us to outline the concept of schizophrenia and to clarify the clinical consequences of brain structure changes.

Brain↗

PubMed2006

Cognitive impairment and functional outcome in schizophrenia and bipolar disorder.

A considerable amount of evidence supports the relationship between cognitive impairment and functional outcomes in schizophrenia. Cognitive impairment is considered a core feature of schizophrenia that includes problems in speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition. These deficits can also serve as an endophenotype for the illness in studies of genetics. Cognition is considered a reasonable treatment target in individuals with schizophrenia, partly because cognitive deficits contribute to poor functional outcomes. Similarly, evidence is beginning to emerge that cognitive impairment may also be a core feature of bipolar disorder. In addition, cognitive deficits adversely affect functional outcomes in bipolar disorder. This evidence suggests that cognition can be considered a reasonable target for intervention in both schizophrenia and bipolar disorder.

Adult↗

PubMedDate not supplied

[Disturbances of social cognition in schizophrenia].

Social cognition is an ability to perceive socially relevant stimuli and to behave accordingly. It is connected with the processing of information brought about by significant social stimuli. Recently, social cognition is a topic of intensive research in psychology, neurosciences and psychiatry. Processes involved in social cognition include: perception of emotion, input of eye contact, reaction to voice prosody or decision-making in social situations. A particular role is played by the mentalizing capabilities (mind-reading) i.e. ability to interpret behaviour of others by attributing them certain mental states. Such an ability is often conceptualized as the Theory of Mind (ToM). This paper is a review of issues connected with disturbances of social cognition in patients with schizophrenia. Deficits in perceptions of face emotion and disturbances of Theory of Mind function in schizophrenia were discussed with special regard to their potential role as endophenotypes of vulnerability to schizophrenia. Also, relations between social cognition and basic neurocognitive processes were presented, as well as the effect on social cognition of different methods of schizophrenia treatment.

Cognition↗

PubMedDate not supplied

[Working memory: neuropsychological and neurobiological issues].

Working memory denotes an ability to remember information for a short-time and to manipulate it. The memory allows including correct information depending on the situation, to keep the information on present activities for a while and enables changing the reaction according to new criteria. The relation between working memory and efficiency of complex cognitive processes and also with the control of emotional processes, plasticity of behaviour and consciousness was demonstrated. Working memory is connected with the activity of the dorsolateral prefrontal cortex of the brain. Recently, it has been shown, that working memory disturbances play an important role in the aetiopathogenesis of psychiatric disturbances such as schizophrenia, bipolar affective disorder or obsessive-compulsive disorder. Working memory disturbances are also shown in a proportion of healthy first-degree relatives of patients with schizophrenia or bipolar disorders. Working memory disturbances are presently regarded as a cognitive endophenotypic marker of vulnerability to these illnesses. In recent years, an association between working memory abilities and activity of different neurotransmitters, especially with the dopaminergic system in the brain, has been shown. Molecular genetic studies show an association between working memory abilities and polymorphism of the dopaminergic system genes in schizophrenia and polymorphism of BDNF gene in bipolar affective disorders. So far not much data about the genetics of working memory in healthy subjects has been gathered. Currently in Poland such research is carried on in the Clinical Neuropsychology Unit Nicolaus Copernicus University, Collegium Medicum in Bydgoszcz in cooperation with the Department of Adult Psychiatry and Laboratory of Psychiatric Genetics University of Medical Sciences in Poznań.

Bipolar Disorder↗

PubMed2006

Cognitive impairment and functional outcome in schizophrenia and bipolar disorder.

Cognitive impairment in schizophrenia and that in bipolar disorder share some similarities. However, more literature exists on cognitive impairment in schizophrenia than in bipolar disorder. The NIMH Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Initiative has identified several cognitive domains that are dysfunctional in schizophrenia and should be considered in the context of clinical trials. Cognitive impairments in these domains are also seen in bipolar disorder, but they tend to be milder. These impairments seem to be a core feature of schizophrenia and exist outside of mood episodes in bipolar disorder. Impairments are present in unaffected relatives of patients with schizophrenia or bipolar disorder, can serve as an endophenotype for both illnesses, and are linked to community functioning.

Bipolar Disorder↗