Formal thought disorders are usually regarded as a central symptom of schizophrenic psychoses, bu... more Formal thought disorders are usually regarded as a central symptom of schizophrenic psychoses, but nevertheless as diagnostically non-specific. Karl Leonhard, therefore, differentiated in his classification of endogenous psychoses between a whole lot of diagnostically specific types of formal thought disorders. He described two psychoses, of which formal thought disorder is the main psychopathological feature, i.e. confusion psychosis and cataphasia. By means of an analysis of tape-recorded utterances of patients with such psychoses we demonstrate the phenomenological differentiation of the distinct types of thought disorder in these psychoses. In confusion psychosis the disturbance concerns the thematic organisation and target-oriented direction of the train of thought. Characteristically, an "incoherence of thematic choice" results, reflecting a disturbance on the level of organisation of discourse. The concepts, ideas and themes itself are organised in a logically correct manner and are comprehensible. The thought disorder in cataphasia, however, shows severe logical faults in the connection of concepts and ideas, as a result of which single themes and ideas become a logical and incomprehensible. Moreover, cataphasic thought disorder goes beyond the level of discourse organisation and extends to disturbances of linguistic functions including mistakes on a semantical and syntactic level. These observations correspond well with the widely accepted assumption of a modular organisation of cognitive and linguistic processes. The thought disorder in prognostically unfavourable cataphasia concerns "basal" logical, semantic and syntactic systems, which remain uninfluenced in the prognostically favourable confusion psychosis. In the latter, therefore, the disorder is restricted to the higher functions of organisation of discourse.
Carl Wernicke derived his theory of the pathomechanism of mental illness of his theories on aphas... more Carl Wernicke derived his theory of the pathomechanism of mental illness of his theories on aphasia. For this reason Jaspers [ 1 ] accused him of mythologizing the brain. On the other hand, however, Jaspers does admit that Wernicke has produced one of the most important works on psychology and says that a serious study of this work is something
Genetic factors have been implicated in the etiology of affective disorders but due to the comple... more Genetic factors have been implicated in the etiology of affective disorders but due to the complex inheritance patterns of these disorders, identification of the responsible gene(s) has so far been unsuccessful. Decreased platelet serotonin (5-HT) transport and reduced binding of imipramine or paroxetine to brain and platelet 5-HT uptake sites~transporters in patients with depression and suicide victims define the 5-HT transporter (5-HTI') as a candidate gene. The primary structure of the 5-HTT was analyzed in 17 patients meeting DSM-IIIoR diagnostic criteria for major depressive or bipolar disorder and in 4 healthy controls using polymerase chain reaction (PCR-) amplification and sequencing of complementary deoxyribose nucleic acid (cDNA) synthes&ed from platelet 5-HTT messenger ribose nucleic acid (mRNA). Direct PCR sequencing of the protein coding region failed to reveal changes in the deduced amino acid sequence of the platelet/brain 5-HTT (40,000 base pairs sequence screen...
SiR-Meloni and colleagues (April 8, p 932) report a positive association between manic-depressive... more SiR-Meloni and colleagues (April 8, p 932) report a positive association between manic-depressive illness (bipolar affective disorder) and a tetranucleotide repeat marker located in a non-coding region (intron 1) of the tyrosine hydroxylase gene. The frequency of genotype BE was significantly increased in French patients (n=64) when compared with that of controls (n=64). The BE genotype was associated with a familial history of affective disorders and/or delusional symptoms during manic or depressive episodes.
On the basis of 24 maternity hospital records, the current study investigated the validity of mat... more On the basis of 24 maternity hospital records, the current study investigated the validity of maternal recall and the relationship of maternal infections during pregnancy and obstetric complications (OCs) to different diagnostic subgroups of endogenous psychoses on which we reported previously in this journal. Maternal recall showed good agreement to maternity hospital records in the Lewis and Murray scale (vartheta = 0.74). With regard to infectious diseases during pregnancy maternal recall and records showed a weaker, but also good correlation (vartheta = 0.18). Psychoses with low genetic loading had more OCs than psychoses with high genetic loading. Maternal infectious diseases, especially during the fourth or fifth month of gestation, were significantly allocated to Leonhard's systematic schizophrenias. Data from maternity hospital records support our report that infectious diseases during midgestation and further perinatal complications seem to be important etiologic factors in systematic forms of schizophrenia without marked familial loading.
Genetic factors have been implicated in the etiology of affective disorders but due to the comple... more Genetic factors have been implicated in the etiology of affective disorders but due to the complex inheritance patterns of these disorders, identification of the responsible gene(s) has so far been unsuccessful. Decreased platelet serotonin (5-HT) transport and reduced binding of imipramine or paroxetine to brain and platelet 5-HT uptake sites~transporters in patients with depression and suicide victims define the 5-HT transporter (5-HTI') as a candidate gene. The primary structure of the 5-HTT was analyzed in 17 patients meeting DSM-IIIoR diagnostic criteria for major depressive or bipolar disorder and in 4 healthy controls using polymerase chain reaction (PCR-) amplification and sequencing of complementary deoxyribose nucleic acid (cDNA) synthes&ed from platelet 5-HTT messenger ribose nucleic acid (mRNA). Direct PCR sequencing of the protein coding region failed to reveal changes in the deduced amino acid sequence of the platelet/brain 5-HTT (40,000 base pairs sequence screened), although a conservative single-base substitution representing a silent polymorphism was found. The results provide preliminary evidence that alterations in the primary structure of 5-HTT are not generally involved in the pathogenesis of unipolar depression and manic-depressive illness.
A possible dysregulation of dopaminergic neurotransmission has been implicated in a variety of ne... more A possible dysregulation of dopaminergic neurotransmission has been implicated in a variety of neuropsychiatric diseases. In the present study we systematically searched for the presence of mutations in the 5'-flanking region of the dopamine D1 receptor (DRD1) gene. This region has previously been shown to contain a functional promoter [Minowa et al., 1992: Proc Natl Acad Sci 89:3045-3049; Minowa et al., 1993: J Biol Chem 268:23544-23551]. We investigated 119 unrelated individuals (including 36 schizophrenic patients, 38 bipolar affective patients, and 45 healthy controls) using single-strand conformation analysis (SSCA). Eleven overlapping PCR fragments covered 2,189 bp of DNA sequence. We identified six single base substitutions: -2218T/C, -2102C/A, -2030T/C, -1992G/A, -1251G/C, and -800T/C. None of the mutations was found to be located in regions which have important influence on the level of transcriptional activity. Allele frequencies were similar in patients and controls, indicating that genetic variation in the 5'-regulatory region of the DRD1 gene is unlikely to play a frequent, major role in the genetic predisposition to either schizophrenia or bipolar affective disorder.
Serotonin receptor type 3 is a ligand-gated ion channel implicated in behavioural disorders. Our ... more Serotonin receptor type 3 is a ligand-gated ion channel implicated in behavioural disorders. Our objective was to identify nucleotide variants in a specific portion of the 5' region of the serotonin receptor gene (HTR3A) containing upstream open reading frames (uORFs) and to investigate their effect on bipolar disease. Mutations in uORFs have been recently shown to cause disease by changing expression on the translational level. We identified one polymorphism, C195T, and one missense mutation, C178T (Pro16Ser) within an upstream open reading frame. No significant association was found between the C195T polymorphism and bipolar affective disorder. A significant association was, however, found between the variant C178T in 156 patients with bipolar disorder compared to 156 healthy controls (P = 0.00016). To investigate the relevance of this variant on gene expression, luciferase reporter constructs containing the C178T (Pro16Ser) allele were established and compared to the C178T plus C195T and wild-type alleles. Reporter constructs containing the C178T (Pro16Ser) allele drove 245% and 138% expression compared to the wild-type allele. These findings show that the C178T(Pro16Ser) variant in HTR3A may represent a functional variant and affect the susceptibility to bipolar disorder.
In a five year follow-up study of 57 hospitalized chronic schizophrenics we investigated the deve... more In a five year follow-up study of 57 hospitalized chronic schizophrenics we investigated the development of symptoms and syndromes, taking into account different nosological concepts. We could demonstrate that after a careful methodological training Leonhard's differentiated classification of schizophrenia is highly reliable. Analyses of the long-term course of individual syndromes showed that a dichotomy into positive and negative symptoms does not provide a reliable prognosis. Within the Leonhard classification, however, a remarkable homogeneity was evident with regard to course and outcome of various schizophrenic subtypes. Investigating the biography of the kinships we found further indication of nosologic heterogeneity, particularly between unsystematic (high hereditary loading) and systematic schizophrenias (almost no hereditary loading). However, the strategy of a simple dichotomy into familial/sporadic cases appears to have too many methodological shortcomings. Further, the study showed that, in this cohort, neuroleptic long-term treatment did not decisively influence the development of residual states, with or without residual marked positive symptoms. It is suggested that the Leonhard classification is a promising concept for further psychopathological as well as biological investigations in psychiatry.
Serotonin receptor genes have always been considered excellent candidate genes in the aetiology o... more Serotonin receptor genes have always been considered excellent candidate genes in the aetiology of neurogenetic diseases. In this study, we assessed sequence variations of the HTR3A gene. For this purpose, we established exon-specific primers and analysed DNA samples from 165 unrelated individuals including 70 schizophrenic patients, 48 patients with bipolar affective disorder and 47 healthy control persons using polymerase chain reaction/single-strand conformational polymorphism analysis. We discovered six sequence variants, five of which represent polymorphisms. These polymorphisms could not be associated with schizophrenia and bipolar affective disorder (P = 0.055-1). We also detected a missense mutation in exon 9 in a schizophrenic patient at a conserved position (Pro391Arg). To determine the incidence of this substitution an extended set of 358 schizophrenic patients and 155 control individuals was investigated. The Pro391Arg mutation was not detected in these schizophrenic patients and controls screened. However, a second missense mutation (Arg344His) was detected in one schizophrenic patient, but not in any of the controls. These results suggest that the observed mutations in HTR3A are rare and therefore do not play a major role in the aetiology of the disorder. Further studies are needed to support the hypothesis that HTR3A may contribute to the schizophrenia in these patients.
... Exogenous harmful effects, predominant during the cold season, may affect the developing imma... more ... Exogenous harmful effects, predominant during the cold season, may affect the developing immature fetal brain and thus constitute some of the factors predisposing to schizophrenic breakdown in adulthood. Neuropathological ...
Several studies show that substance dependence disorders are characterized by an enhanced process... more Several studies show that substance dependence disorders are characterized by an enhanced processing of substance-related stimuli. The present study was designed to examine the association between craving levels and selective processing of drug cues in cocaine-dependent patients using event-related brain potentials (ERPs). In abstinent cocaine-dependent patients and a healthy control group, we studied the late positive potential (LPP) amplitudes elicited by neutral and cocaine-related stimuli. The results show that cocaine-dependent patients have an enhanced electrophysiological response in the late LPP time window to cocaine-related stimuli as compared to controls, suggesting an enhanced processing of these stimuli. Most importantly, a robust association was observed between cocaine craving and LPP amplitude. High craving levels were associated with larger LPP amplitudes at central electrode sites in the right hemisphere. These findings are in line with theories linking motivational aspects and appetitive stimulus processing. Furthermore, it is demonstrated that ERPs are a useful index to assess motivational properties of stimuli in cocaine-dependent patients. These findings suggest that electrophysiological measures may have clinical relevance in substance use disorders.
European Archives of Psychiatry and Clinical Neuroscience, May 1, 1995
In a family study involving 139 probands with DSM-III-R catatonic schizophrenia and 543 first-deg... more In a family study involving 139 probands with DSM-III-R catatonic schizophrenia and 543 first-degree relatives, we investigated age-specific morbidity risk according to Leonhard's clinical distinction between systematic and periodic catatonia. This dichotomy is based on different types of symptomatology, course, and outcome. In systematic catatonia the age-corrected morbidity risk was 4.6%. In periodic catatonia, however, there was an age-corrected morbidity risk with homogenous psychoses of 26.9%, and more parents than siblings were affected. This points strongly to a major gene effect in periodic catatonia. Furthermore, a pairwise comparison of patients and their parents revealed patterns of anticipation, i.e., the probands' age at the onset of disease was significantly earlier than that of their parents (P < 0.001). Similarly, anticipation was apparent in pedigrees with three successive generations affected. This inheritance pattern with homogenous psychoses and anticipation indicates that genes with trinucleotid repeat expansion or other repetitive elements affecting gene expression may be involved in the etiology of periodic catatonia. Thus, periodic catatonia as a specific clinical subtype of schizophrenia is a promising candidate for molecular genetic evaluation.
One reason for the inconsistent findings in schizophrenia research is the lack of diagnostic conf... more One reason for the inconsistent findings in schizophrenia research is the lack of diagnostic conformity. In the face of modern operational "atheoretical" diagnostic systems, this dilemma is still present. In order to examine specificity and validity of diagnoses, we carried out a systematic twin study with index twins suffering from schizophrenic spectrum psychoses. We compared the diagnostic systems of DSM-III-R, which is based on consensus of international experts, with Leonhards' nosology developed on sophisticated clinical observation and description of psychopathological phenomena occurring during the long-term course of psychiatric diseases. We examined twin concordance, family history, and the frequency and severity of complications of pregnancy and child-birth. The results suggest that the schizophrenic spectrum has to be divided into clinically and etiologically heterogeneous subgroups. This was much more striking when Leonhard's diagnostic criteria were used than with DSM-III-R diagnostic criteria. There seem to be three valid and etiologically different groups: cycloid psychoses, unsystematic schizophrenias and systematic schizophrenias as proposed by Leonhard. In cycloid psychoses genetic loading seems to be low (proband concordance MZ 38%, DZ 29%), but pregnancy and birth complications may have an important role in the etiology. On the other hand, unsystematic schizophrenias are obviously predominantly inherited (proband concordance MZ 88%, DZ 17%) and "environmental" factors are not very prominent. It is striking that MZ twins with a diagnosis of systematic schizophrenia have not yet been found, whereas 32% of DZ index twins (6 out of 19) were diagnosed as having systematic schizophrenia. Further, all DZ twins with the diagnosis of systematic schizophrenia were discordant and the affected twins had threetimes as many and as severe pregnancy and birth complications in the history than their healthy co-twins.
Fortschritte Der Neurologie Psychiatrie, Feb 1, 1993
In 1299 DSM III-R schizophrenics a slight excess of winter and spring births was evident when com... more In 1299 DSM III-R schizophrenics a slight excess of winter and spring births was evident when compared to the general population. However, when patients were allocated to different diagnostic subgroups according to the Leonhard classification this remained true only for those forms without obvious genetic loading (cycloid psychoses and systematic schizophrenias). On the contrary those forms with high genetic loading (unsystematic schizophrenias) showed a clearcut decrease of births in these months. This decrease, however, was significantly caused by periodic catatonics and cataphasics, but not by affect-laden paraphrenics. The findings corroborate the hypothesis that exogenous noxious agents, present in a crucial period of brain maturation, may be of etiological significance in schizophrenia with low genetic loading. Further, it was suggested that in some foetuses at high genetic risk for the disorder more abortions, stillbirths, postnatal deaths and early childhood deaths can occur, if additional exogenous noxious agents affect these individuals.
Formal thought disorders are usually regarded as a central symptom of schizophrenic psychoses, bu... more Formal thought disorders are usually regarded as a central symptom of schizophrenic psychoses, but nevertheless as diagnostically non-specific. Karl Leonhard, therefore, differentiated in his classification of endogenous psychoses between a whole lot of diagnostically specific types of formal thought disorders. He described two psychoses, of which formal thought disorder is the main psychopathological feature, i.e. confusion psychosis and cataphasia. By means of an analysis of tape-recorded utterances of patients with such psychoses we demonstrate the phenomenological differentiation of the distinct types of thought disorder in these psychoses. In confusion psychosis the disturbance concerns the thematic organisation and target-oriented direction of the train of thought. Characteristically, an &quot;incoherence of thematic choice&quot; results, reflecting a disturbance on the level of organisation of discourse. The concepts, ideas and themes itself are organised in a logically correct manner and are comprehensible. The thought disorder in cataphasia, however, shows severe logical faults in the connection of concepts and ideas, as a result of which single themes and ideas become a logical and incomprehensible. Moreover, cataphasic thought disorder goes beyond the level of discourse organisation and extends to disturbances of linguistic functions including mistakes on a semantical and syntactic level. These observations correspond well with the widely accepted assumption of a modular organisation of cognitive and linguistic processes. The thought disorder in prognostically unfavourable cataphasia concerns &quot;basal&quot; logical, semantic and syntactic systems, which remain uninfluenced in the prognostically favourable confusion psychosis. In the latter, therefore, the disorder is restricted to the higher functions of organisation of discourse.
Carl Wernicke derived his theory of the pathomechanism of mental illness of his theories on aphas... more Carl Wernicke derived his theory of the pathomechanism of mental illness of his theories on aphasia. For this reason Jaspers [ 1 ] accused him of mythologizing the brain. On the other hand, however, Jaspers does admit that Wernicke has produced one of the most important works on psychology and says that a serious study of this work is something
Genetic factors have been implicated in the etiology of affective disorders but due to the comple... more Genetic factors have been implicated in the etiology of affective disorders but due to the complex inheritance patterns of these disorders, identification of the responsible gene(s) has so far been unsuccessful. Decreased platelet serotonin (5-HT) transport and reduced binding of imipramine or paroxetine to brain and platelet 5-HT uptake sites~transporters in patients with depression and suicide victims define the 5-HT transporter (5-HTI') as a candidate gene. The primary structure of the 5-HTT was analyzed in 17 patients meeting DSM-IIIoR diagnostic criteria for major depressive or bipolar disorder and in 4 healthy controls using polymerase chain reaction (PCR-) amplification and sequencing of complementary deoxyribose nucleic acid (cDNA) synthes&ed from platelet 5-HTT messenger ribose nucleic acid (mRNA). Direct PCR sequencing of the protein coding region failed to reveal changes in the deduced amino acid sequence of the platelet/brain 5-HTT (40,000 base pairs sequence screen...
SiR-Meloni and colleagues (April 8, p 932) report a positive association between manic-depressive... more SiR-Meloni and colleagues (April 8, p 932) report a positive association between manic-depressive illness (bipolar affective disorder) and a tetranucleotide repeat marker located in a non-coding region (intron 1) of the tyrosine hydroxylase gene. The frequency of genotype BE was significantly increased in French patients (n=64) when compared with that of controls (n=64). The BE genotype was associated with a familial history of affective disorders and/or delusional symptoms during manic or depressive episodes.
On the basis of 24 maternity hospital records, the current study investigated the validity of mat... more On the basis of 24 maternity hospital records, the current study investigated the validity of maternal recall and the relationship of maternal infections during pregnancy and obstetric complications (OCs) to different diagnostic subgroups of endogenous psychoses on which we reported previously in this journal. Maternal recall showed good agreement to maternity hospital records in the Lewis and Murray scale (vartheta = 0.74). With regard to infectious diseases during pregnancy maternal recall and records showed a weaker, but also good correlation (vartheta = 0.18). Psychoses with low genetic loading had more OCs than psychoses with high genetic loading. Maternal infectious diseases, especially during the fourth or fifth month of gestation, were significantly allocated to Leonhard&#39;s systematic schizophrenias. Data from maternity hospital records support our report that infectious diseases during midgestation and further perinatal complications seem to be important etiologic factors in systematic forms of schizophrenia without marked familial loading.
Genetic factors have been implicated in the etiology of affective disorders but due to the comple... more Genetic factors have been implicated in the etiology of affective disorders but due to the complex inheritance patterns of these disorders, identification of the responsible gene(s) has so far been unsuccessful. Decreased platelet serotonin (5-HT) transport and reduced binding of imipramine or paroxetine to brain and platelet 5-HT uptake sites~transporters in patients with depression and suicide victims define the 5-HT transporter (5-HTI') as a candidate gene. The primary structure of the 5-HTT was analyzed in 17 patients meeting DSM-IIIoR diagnostic criteria for major depressive or bipolar disorder and in 4 healthy controls using polymerase chain reaction (PCR-) amplification and sequencing of complementary deoxyribose nucleic acid (cDNA) synthes&ed from platelet 5-HTT messenger ribose nucleic acid (mRNA). Direct PCR sequencing of the protein coding region failed to reveal changes in the deduced amino acid sequence of the platelet/brain 5-HTT (40,000 base pairs sequence screened), although a conservative single-base substitution representing a silent polymorphism was found. The results provide preliminary evidence that alterations in the primary structure of 5-HTT are not generally involved in the pathogenesis of unipolar depression and manic-depressive illness.
A possible dysregulation of dopaminergic neurotransmission has been implicated in a variety of ne... more A possible dysregulation of dopaminergic neurotransmission has been implicated in a variety of neuropsychiatric diseases. In the present study we systematically searched for the presence of mutations in the 5&amp;amp;amp;amp;amp;amp;#39;-flanking region of the dopamine D1 receptor (DRD1) gene. This region has previously been shown to contain a functional promoter [Minowa et al., 1992: Proc Natl Acad Sci 89:3045-3049; Minowa et al., 1993: J Biol Chem 268:23544-23551]. We investigated 119 unrelated individuals (including 36 schizophrenic patients, 38 bipolar affective patients, and 45 healthy controls) using single-strand conformation analysis (SSCA). Eleven overlapping PCR fragments covered 2,189 bp of DNA sequence. We identified six single base substitutions: -2218T/C, -2102C/A, -2030T/C, -1992G/A, -1251G/C, and -800T/C. None of the mutations was found to be located in regions which have important influence on the level of transcriptional activity. Allele frequencies were similar in patients and controls, indicating that genetic variation in the 5&amp;amp;amp;amp;amp;amp;#39;-regulatory region of the DRD1 gene is unlikely to play a frequent, major role in the genetic predisposition to either schizophrenia or bipolar affective disorder.
Serotonin receptor type 3 is a ligand-gated ion channel implicated in behavioural disorders. Our ... more Serotonin receptor type 3 is a ligand-gated ion channel implicated in behavioural disorders. Our objective was to identify nucleotide variants in a specific portion of the 5&amp;amp;amp;amp;amp;amp;amp;amp;#39; region of the serotonin receptor gene (HTR3A) containing upstream open reading frames (uORFs) and to investigate their effect on bipolar disease. Mutations in uORFs have been recently shown to cause disease by changing expression on the translational level. We identified one polymorphism, C195T, and one missense mutation, C178T (Pro16Ser) within an upstream open reading frame. No significant association was found between the C195T polymorphism and bipolar affective disorder. A significant association was, however, found between the variant C178T in 156 patients with bipolar disorder compared to 156 healthy controls (P = 0.00016). To investigate the relevance of this variant on gene expression, luciferase reporter constructs containing the C178T (Pro16Ser) allele were established and compared to the C178T plus C195T and wild-type alleles. Reporter constructs containing the C178T (Pro16Ser) allele drove 245% and 138% expression compared to the wild-type allele. These findings show that the C178T(Pro16Ser) variant in HTR3A may represent a functional variant and affect the susceptibility to bipolar disorder.
In a five year follow-up study of 57 hospitalized chronic schizophrenics we investigated the deve... more In a five year follow-up study of 57 hospitalized chronic schizophrenics we investigated the development of symptoms and syndromes, taking into account different nosological concepts. We could demonstrate that after a careful methodological training Leonhard&#39;s differentiated classification of schizophrenia is highly reliable. Analyses of the long-term course of individual syndromes showed that a dichotomy into positive and negative symptoms does not provide a reliable prognosis. Within the Leonhard classification, however, a remarkable homogeneity was evident with regard to course and outcome of various schizophrenic subtypes. Investigating the biography of the kinships we found further indication of nosologic heterogeneity, particularly between unsystematic (high hereditary loading) and systematic schizophrenias (almost no hereditary loading). However, the strategy of a simple dichotomy into familial/sporadic cases appears to have too many methodological shortcomings. Further, the study showed that, in this cohort, neuroleptic long-term treatment did not decisively influence the development of residual states, with or without residual marked positive symptoms. It is suggested that the Leonhard classification is a promising concept for further psychopathological as well as biological investigations in psychiatry.
Serotonin receptor genes have always been considered excellent candidate genes in the aetiology o... more Serotonin receptor genes have always been considered excellent candidate genes in the aetiology of neurogenetic diseases. In this study, we assessed sequence variations of the HTR3A gene. For this purpose, we established exon-specific primers and analysed DNA samples from 165 unrelated individuals including 70 schizophrenic patients, 48 patients with bipolar affective disorder and 47 healthy control persons using polymerase chain reaction/single-strand conformational polymorphism analysis. We discovered six sequence variants, five of which represent polymorphisms. These polymorphisms could not be associated with schizophrenia and bipolar affective disorder (P = 0.055-1). We also detected a missense mutation in exon 9 in a schizophrenic patient at a conserved position (Pro391Arg). To determine the incidence of this substitution an extended set of 358 schizophrenic patients and 155 control individuals was investigated. The Pro391Arg mutation was not detected in these schizophrenic patients and controls screened. However, a second missense mutation (Arg344His) was detected in one schizophrenic patient, but not in any of the controls. These results suggest that the observed mutations in HTR3A are rare and therefore do not play a major role in the aetiology of the disorder. Further studies are needed to support the hypothesis that HTR3A may contribute to the schizophrenia in these patients.
... Exogenous harmful effects, predominant during the cold season, may affect the developing imma... more ... Exogenous harmful effects, predominant during the cold season, may affect the developing immature fetal brain and thus constitute some of the factors predisposing to schizophrenic breakdown in adulthood. Neuropathological ...
Several studies show that substance dependence disorders are characterized by an enhanced process... more Several studies show that substance dependence disorders are characterized by an enhanced processing of substance-related stimuli. The present study was designed to examine the association between craving levels and selective processing of drug cues in cocaine-dependent patients using event-related brain potentials (ERPs). In abstinent cocaine-dependent patients and a healthy control group, we studied the late positive potential (LPP) amplitudes elicited by neutral and cocaine-related stimuli. The results show that cocaine-dependent patients have an enhanced electrophysiological response in the late LPP time window to cocaine-related stimuli as compared to controls, suggesting an enhanced processing of these stimuli. Most importantly, a robust association was observed between cocaine craving and LPP amplitude. High craving levels were associated with larger LPP amplitudes at central electrode sites in the right hemisphere. These findings are in line with theories linking motivational aspects and appetitive stimulus processing. Furthermore, it is demonstrated that ERPs are a useful index to assess motivational properties of stimuli in cocaine-dependent patients. These findings suggest that electrophysiological measures may have clinical relevance in substance use disorders.
European Archives of Psychiatry and Clinical Neuroscience, May 1, 1995
In a family study involving 139 probands with DSM-III-R catatonic schizophrenia and 543 first-deg... more In a family study involving 139 probands with DSM-III-R catatonic schizophrenia and 543 first-degree relatives, we investigated age-specific morbidity risk according to Leonhard's clinical distinction between systematic and periodic catatonia. This dichotomy is based on different types of symptomatology, course, and outcome. In systematic catatonia the age-corrected morbidity risk was 4.6%. In periodic catatonia, however, there was an age-corrected morbidity risk with homogenous psychoses of 26.9%, and more parents than siblings were affected. This points strongly to a major gene effect in periodic catatonia. Furthermore, a pairwise comparison of patients and their parents revealed patterns of anticipation, i.e., the probands' age at the onset of disease was significantly earlier than that of their parents (P < 0.001). Similarly, anticipation was apparent in pedigrees with three successive generations affected. This inheritance pattern with homogenous psychoses and anticipation indicates that genes with trinucleotid repeat expansion or other repetitive elements affecting gene expression may be involved in the etiology of periodic catatonia. Thus, periodic catatonia as a specific clinical subtype of schizophrenia is a promising candidate for molecular genetic evaluation.
One reason for the inconsistent findings in schizophrenia research is the lack of diagnostic conf... more One reason for the inconsistent findings in schizophrenia research is the lack of diagnostic conformity. In the face of modern operational "atheoretical" diagnostic systems, this dilemma is still present. In order to examine specificity and validity of diagnoses, we carried out a systematic twin study with index twins suffering from schizophrenic spectrum psychoses. We compared the diagnostic systems of DSM-III-R, which is based on consensus of international experts, with Leonhards' nosology developed on sophisticated clinical observation and description of psychopathological phenomena occurring during the long-term course of psychiatric diseases. We examined twin concordance, family history, and the frequency and severity of complications of pregnancy and child-birth. The results suggest that the schizophrenic spectrum has to be divided into clinically and etiologically heterogeneous subgroups. This was much more striking when Leonhard's diagnostic criteria were used than with DSM-III-R diagnostic criteria. There seem to be three valid and etiologically different groups: cycloid psychoses, unsystematic schizophrenias and systematic schizophrenias as proposed by Leonhard. In cycloid psychoses genetic loading seems to be low (proband concordance MZ 38%, DZ 29%), but pregnancy and birth complications may have an important role in the etiology. On the other hand, unsystematic schizophrenias are obviously predominantly inherited (proband concordance MZ 88%, DZ 17%) and "environmental" factors are not very prominent. It is striking that MZ twins with a diagnosis of systematic schizophrenia have not yet been found, whereas 32% of DZ index twins (6 out of 19) were diagnosed as having systematic schizophrenia. Further, all DZ twins with the diagnosis of systematic schizophrenia were discordant and the affected twins had threetimes as many and as severe pregnancy and birth complications in the history than their healthy co-twins.
Fortschritte Der Neurologie Psychiatrie, Feb 1, 1993
In 1299 DSM III-R schizophrenics a slight excess of winter and spring births was evident when com... more In 1299 DSM III-R schizophrenics a slight excess of winter and spring births was evident when compared to the general population. However, when patients were allocated to different diagnostic subgroups according to the Leonhard classification this remained true only for those forms without obvious genetic loading (cycloid psychoses and systematic schizophrenias). On the contrary those forms with high genetic loading (unsystematic schizophrenias) showed a clearcut decrease of births in these months. This decrease, however, was significantly caused by periodic catatonics and cataphasics, but not by affect-laden paraphrenics. The findings corroborate the hypothesis that exogenous noxious agents, present in a crucial period of brain maturation, may be of etiological significance in schizophrenia with low genetic loading. Further, it was suggested that in some foetuses at high genetic risk for the disorder more abortions, stillbirths, postnatal deaths and early childhood deaths can occur, if additional exogenous noxious agents affect these individuals.
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Papers by Ernst Franzek