Intra- and interhemispheric electroencephalogram coherence in siblings discordant for schizophrenia and healthy volunteers.

Former studies had pointed to an increased electroencephalogram (EEG) coherence in schizophrenics, but it remained unsolved whether this deviation represents the premorbid state or is only a consequence of the current or previous schizophrenic episodes. To clarify this question, we tested the hypothesis that subjects at elevated risk also reveal higher coherences compared to healthy controls. For that, intra- and interhemispheric EEG coherences were investigated in untreated schizophrenics, their healthy siblings, and healthy controls. Differences were only found regarding the intrahemispheric coherences. Both in schizophrenics and, even though to a lesser degree, in their siblings significantly higher coherence estimates were found compared to the control group. The results are in accordance with the assumption that schizophrenia is predominantly a neurodevelopmental disease. Increased coherence might be assumed to be a vulnerability marker for schizophrenia reflecting maldevelopment of the brain before onset of the disorder.

DAT1 gene polymorphism in alcoholism: a family-based association study.

BACKGROUND: The present study tests the hypothesis that the 9-repeat allele of the dopamine transporter gene (DAT1; SLC6A3) is more frequent in alcohol-dependent probands--and in particular those with severe withdrawal symptoms (seizures and/or delirium)--compared to nonalcoholics. METHODS: To avoid stratification effects, the family-based association approach of Falk and Rubinstein was used in our sample of 87 alcohol-dependent probands and their biological parents. RESULTS: By applying a family-based association approach, we were not able to detect significant association between allele 9 at DAT1 (SLC6A3) and alcoholism as well as between patients with or without severe withdrawal symptoms. CONCLUSIONS: Based on our data, the impact of the 9-repeat allele of the dopamine transporter gene in alcoholism and the severity of alcohol withdrawal symptoms is putatively not substantial.

Allelic variants of dopamine receptor D4 (DRD4) and serotonin receptor 5HT2c (HTR2c) and temperament factors: replication tests.

The contribution of genetic factors to personality differences between individuals is evidenced by twin and adoption studies. Ebstein et al. [1996, 1997a, 1997b] reported an association between the long repeat allele of the dopamine D4-exon-III receptor polymorphism and the human personality dimension novelty seeking (NS), between the 5HT2c-ser-23 allele and reward dependence, and an interaction between both receptor polymorphisms and reward dependence. Subsequent replication tests mainly reported controversial results for the association between DRD4-exon-III long repeat and NS. We examined a homogeneous study population of 190 healthy male students of middle European descent, aged between 20 and 30 years using Cloninger's TPQ in order to replicate Ebstein's findings. Using a significance level of 1%, no association between the long repeat of the DRD4-exon-III polymorphism and NS and between the 5HT2c receptor polymorphism and reward dependence was found, but a significant interaction effect of DRD4 and 5HT2c receptor polymorphisms on reward dependence was observed in accordance to Ebstein's report.

Fragile-X carrier females: evidence for a distinct psychopathological phenotype?

The present study examined 35 mothers (29 premutation carriers) of children with fragile-X syndrome in measures of intelligence and psychiatric disorders by comparing them with two control groups: a) 30 mothers of children in the general population and b) 17 mothers of non-fra-X retarded children with autism. Premutation carriers had a higher frequency of affective disorders than mothers from the general population. Preliminary data indicate that normally intelligent premutation carriers of the fra-X genetic abnormality have a similar frequency of affective disorders (DSM-III-R criteria [APA, 1987]) than mothers of autistic children. Neither carriers of the premutation nor carriers of the full mutation in the fra-X group obtained a diagnosis of the schizophrenia-spectrum (schizophrenia, schizophreniform disorder, and schizoaffective disorder). Carriers of the fra-X full mutation had considerably lower IQ than carriers of the fra-X premutation. There was a negative correlation between length of CGG repeats and IQ which failed to reach significance in both groups of fra-X carriers. Psychiatric morbidity was not restricted to carriers of the fra-X full mutation only but was also present in normal intelligent premutation carriers. Furthermore the age of onset of psychiatric morbidity in both groups of mothers of fra-X children as well as the group of mothers with autistic children was much earlier than the age when mental retardation had been diagnosed in their children. Increased psychosocial burden of raising a developmentally retarded child and/or feelings of guilt of being a fra-X carrier can therefore not fully explain our findings (three-fold higher frequencies of affective disorders compared to mothers from the general population).

The relationship between major and subthreshold variants of unipolar depression.

Recent epidemiological research in the general population and primary care demonstrated that a substantial proportion of disabling depressive syndromes do not meet the diagnostic criteria for major depression. This observation proposes less restrictive diagnostic definitions of depression. However, a gain in sensitivity may induce a substantial loss of specificity. A variety of diagnostic definitions of subthreshold depression has been proposed balancing both aspects. However, the less restrictive diagnostic definitions are, the lower the specificity. This report explores variants of subthreshold depression characterized by current and subsequent disability in a prospectively investigated sample of general practice patients (n = 400), recruited within the framework of the WHO study "Psychological Problems in Primary Care and a survey in the general population. Duration of episodes, recurrence and number of associated symptoms are the main diagnostic variables. Brief depression with multiple episodes per year (including recurrent brief depression as defined by ICD-10) is comparable to major depression by social disability and subsequent course in the sample under study.

Gender differences in the prevalence of depression: a survey in primary care.

Epidemiological surveys demonstrate that unipolar depression is more common in females than in males. Gender-specific cultural and social factors may contribute to the female preponderance. This study explores this possibility in a cross-cultural sample of general-practice patients systematically recruited in the WHO study "Psychological Problems in Primary Care" conducted in 14 countries with identical sampling and assessment strategies. Although absolute prevalence rates are broadly varying between centers proposing that the gender ratio is nearly constant with 1:2. The cultural context does not contribute substantially to the female preponderance. This study lends some support to previous observations that the magnitude of female preponderance is associated with the number of symptoms associated with depression requested for caseness and inversely related to the degree of social impairment. Matching social role variables (marital status, children, occupational status) between females and males reduces the female excess by about 50% across all centers. Therefore, we conclude that social factors are inducing part of the preponderance of females among depressed cases.

Genotype-phenotype relationship in female carriers of the premutation and full mutation of FMR-1.

The present French-German cooperative study focuses on the genotype-phenotype relationship of mutations of the FMR-1 gene and psychiatric conditions in mothers with a full mutation in the FMR-1 gene of fra-X children (n=13), mothers with a premutation in the FMR-1 gene of fra-X children (n=61), as well as premutated siblings of these mothers without affected children (n=17) and two non-mutated control groups: (1) siblings of these mothers with normal CGG repeat (n=18); and (2) mothers of non-fra-X autistic children (n=42). Mothers with a full mutation in the FMR-1 gene and mothers with a premutation in the FMR-1 gene did not differ in the frequency of any axis I disorder; however, both groups were diagnosed with social phobia more often than the control group of mothers of autistic children. Moreover, mothers with a premutation in the FMR-1 gene of fra-X children and their siblings with the premutation (without affected offspring) revealed a similar frequency of social phobia. Furthermore avoidant personality disorder was more common in groups of carriers of the full premutation than in siblings without mutation or than the control group of mothers with autistic children. On the basis of our data, we therefore suggest that social avoidance (expressed as social phobia or avoidant personality disorder) has been underestimated in previous studies of carriers with the FMR-1 full mutation or premutation. Comorbidity of axis I and axis II psychiatric diagnoses was mainly restricted to the group of carriers of the full mutation and carriers of the premutation of FMR-1. Correlations between size of CGG repeat and IQ as well as CGG and age of onset of axis I diagnosis were non-significant. IQ of subjects had no impact on presence or absence of axis I and/or axis II diagnoses.

Differential memory span--abnormal lateralization pattern in schizophrenic patients and their siblings?

The recurring digit span test is hypothesized to assess consolidation memory and hypothetically addresses neuropsychological left-temporohippocampal functioning, an area of the brain which is presumed to play a crucial role in schizophrenia. The present study applied the recurring digit span memory test and the recurring block span memory test (assumed to be an indicator of right-temporohippocampal functioning) to 106 acute schizophrenic patients (DSM-III-R), 49 siblings of these patients without DSM-III-R lifetime diagnoses as well as 53 non-related control subjects without DSM-III-R lifetime diagnoses. Results of our investigation indicate that schizophrenic patients differ from control subjects regarding recurring digit span in a reduced number of correct reproductions of recurring trials. Since performance of schizophrenic patients was only non-significantly different from control subjects regarding recurring block span memory, our findings point to a task-specific memory impairment in schizophrenia and argue against a generalized deficit in this disease. Furthermore, individuals at risk for schizophrenia also differed from control subjects concerning the recurring digit span memory test but not with regard to the recurring block span test. Therefore we conclude that the reduced cumulative learning curve of verbal material (reduced number of correct reproduction of recurring digit trials) in schizophrenic patients and their healthy siblings might represent a marker for the liability to schizophrenia and parallels neuroimaging findings concerning left-sided temporohippocampal abnormalities in this disease, which presumably play a key role in the etiology of schizophrenia.

[Psychiatric comorbidity in risk groups of opioid addiction: a comparison between opioid dependent and non-opioid dependent prisoners (in jail due to the German narcotics law)]. / Psychiatrische Komorbidität in Risikogruppen für Opiatabhängigkeit: eine Untersuchung an opiatabhängigen und nichtopiatabhängigen BtmG-Inhaftierten.

Individuals who do not develop opioid dependence although they have access to opioids might differ with regard to psychiatric risk factors from opioid-exposed subjects who developed opioid dependence. To test this assumption, the present investigation compared individuals who were in jail due to the German "Dangerous Drugs Act" (i. e. particular risk group due to facilitated opioid availability) according to presence or absence of opioid dependence and psychiatric comorbidity in each group. This study design is in line with the assumption that in addition to the (postulated) environmental risk factor of facilitated availability of opioids, psychiatric risk factors enhance the likelihood for the development of opioid dependence. Opioid addicts represent a risk group, not only for other forms of substance dependence, but also psychiatric disorders like anxiety disorders, suicide attempts and specific forms of personality disorders. However the difference between opioid dependent subjects and non-opioid dependent controls was less marked than initially postulated. Alcoholism of non-opioid dependent prisoners also was associated with depressive episodes, anxiety disorders as well as cocaine dependence. Despite the high frequency of life-time psychiatric comorbidity in the opioid dependent sample, this increased comorbidity was not paralleled by psychiatric treatment. In general, the sample of prisoners investigated here, was characterized by a high frequency of psychiatric disorders including substance dependence.

The relationship between dimensions of alexithymia and dissociation.

BACKGROUND: The study investigated the following hypotheses: (1) Alexithymia is significantly associated with dissociation. (2) Pathological versus nonpathological dissociation is associated with alexithymic traits. METHODS: Psychiatric in- and outpatients (n = 173) and nonclinical subjects (n = 38) were investigated with the Toronto Alexithymia Scale (TAS-20), the FDS (German version of Dissociation Experience Scale) and the Symptom Check List (SCL-90-R; GSI). Correlation analyses followed by MANOVA and logistic regression were performed. RESULTS: Significant correlations and partial correlations, controlling for GSI, were observed between dissociation and alexithymia. The MANOVA demonstrated significantly higher scores for the two TAS-20 dimensions 'difficulty identifying feelings' and 'difficulty expressing feelings' in the group with pathological dissociation. On the basis of the TAS-20 subscores, logistic regression analysis correctly classified 72.5% of the cases into the pathological and the nonpathological dissociation group. CONCLUSIONS: These results support our hypothesis that pathological traits of dissociation are highly associated with alexithymia. A model is discussed in which alexithymic characteristics may contribute to the development of pathological dissociation and stress-related disorders such as posttraumatic stress disorder.

Personality patterns in subjects at risk for affective disorders.

The main conclusions of this study on the familial links between personality patterns and affective disorders are: (1) The personality features with the greatest degree of symptomatic overlap with unipolar depression were more common among the first-degree relatives of probands with this diagnosis: thus dysthymic temperament and neuroticism are enhanced in this group of relatives compared to controls. Likewise personality features with a high degree of symptomatic overlap with bipolar affective disorder were more common among the first-degree relatives of probands with this diagnosis. Thus levels of dysthymic and cyclothymic temperament were elevated in this group of relatives compared to controls, whereas a familial link between neuroticism and bipolar disorder was not observed. (2) In addition, personality traits with only limited similarity with the syndromes of depression and mania were also found to be linked with affective disorders (obsessive-compulsive PD to bipolar disorders, rigidity to both subtypes of affective disorders). These associations have different implications regarding the association between personality/temperament conditions and disorders depending on the degree of overlap between symptoms and the personality trait. Those with substantial overlap may indicate the presence of a unitary disease process in which the enhancement of subthreshold affective traits may result in aggravation of behavior characteristics fulfilling the criteria of fullblown episodes of the disease. This relationship was particularly stressed by Kraepelin, Kretschmer, Clayton et al. and Akiskal. In this view personality and temperament patterns represent minor variants of the associate acute disorders. On the other hand, the relationship between dissimilar conditions may indicate the presence of a risk of underlying vulnerability factors which led to affective disorder only in the presence of additional risk factors. An example of the latter relationship in the present study is the aggregation of obsessive-compulsive and anancastic traits in families with affective disorders. Tellenbach focussed on this particular constellation. Epidemiological and family studies including these personality traits are too rare to fully appreciate the relevance of this particular relationship. Future prospective studies and family genetic studies which investigate the relationship between temperament, personality traits and disorders and affective syndromes are clearly indicated by the results presented herein.

Brief depression among patients in general practice. Prevalence and variation by recurrence and severity.

Depression with substantial psychosocial impairment, but not qualifying as depressive disorder according to the standard diagnostic manuals, is frequent among primary care patients. Recurrent brief depression (RBD) is a diagnostic category intended to identify a major proportion of this group of patients. The WHO study on "Psychological Problems in Primary Health Care" was used as a vehicle to estimate the proportion of patients with this diagnosis and to evaluate the validity of this diagnosis as well as of alternative concepts of brief depression with multiple episodes. This study applies a two-stage sampling scheme; 300 patients also underwent an additional interview tailored for variants of brief depression. 7.6% of primary care patients were identified as RBD with the majority not receiving any other psychiatric diagnosis (DSM-III-R). These patients reported substantial psychosocial impairment, and the majority were identified as psychological cases by general practitioners. However, patients experiencing other variants of brief episodes were also found to be substantially psychosocially impaired, although they were not identified as psychiatric cases by DSM-III-R. Thus, a less restrictive definition of RBD is proposed. The diagnostic definition of RBD has a major impact on the sex ratio of cases: the less restrictive the diagnosis, the more balanced are the prevalence rates between males and females.

Recurrent brief depression in general practice. Clinical features, comorbidity with other disorders, and need for treatment.

This study tested the clinical validity of the new diagnostic entity "recurrent brief depression" (RBD) in 300 general practice patients who participated in the WHO study on "Psychological Problems in Primary Care." Patients with current RBD reported of episodes major depression more often than did a comparison group of nondepressed general practice patients: however, the majority of RBD patients had not received a diagnostic of any well-established affective disorder during the last 12 months. RBD patients (without MDE) did not suffer more frequently from dysthymia, from nonaffective psychiatric disorders, or from somatic disorders. However, RBD was associated with a higher percentage of previous suicide attempts and of ideation of suicide and death. RBD was accompanied by substantial psychosocial impairment; psychosocial impairment in RBD patients could not be explained by excess comorbidity. Thus, the clinical validity of RBD was demonstrated although doubts about the appropriateness of the definition remained. This new diagnostic category needs more attention as only as small minority of patients with RBD received specific antidepressant treatment.

Generalized anxiety disorder (ICD-10) in primary care from a cross-cultural perspective: a valid diagnostic entity?

OBJECTIVE: Generalized anxiety disorder (GAD) is a common psychiatric disorder. The nosological status of this diagnostic entity was critically discussed because of the very high rate of comorbidity with other psychiatric disorders, the assumed low degree of social disability associated with GAD in the absence of other disorders, and an ambigious definition. METHOD: We explored the frequency and associated social disability of GAD, and examined whether the ICD-10 definition of GAD is appropriate. The analysis was based on the WHO study on 'Psychological Problems in Primary Care' conducted in a standardized manner in 14 countries. RESULTS: We found GAD (total and without another psychiatric disorder) to be common in primary care in nearly all countries (mean 1-month prevalence rate, 7.9%), with about 25% of these cases presenting with GAD in the absence of any comorbid psychiatric disorder. GAD in general, as well as non-comorbid GAD, are associated with social disability which is as severe as that in chronic somatic diseases. CONCLUSION: It remains questionable whether the current ICD-10 diagnosis of GAD defining 6 months as a minimum duration and requiring at least four associated symptoms for diagnosis is the most appropriate option. Using this definition, a substantial proportion of psychosocially disabled subjects characterized by anxiety, tension and worrying remain undetected, and are possibly therefore not adequately treated.

Dissociative symptoms in obsessive-compulsive dimensions.

Previous studies have described co-occurrence between obsessive-compulsive disorder (OCD) and dissociation. We intended to evaluate the phenomenological association between different obsessive-compulsive and dissociative symptoms more precisely. Seventy patients with OCD (DSM-IV) were evaluated with the Hamburg Obsessive-Compulsive Inventory (HZI) and the Dissociation Experience Scale. Correlation and discriminant analysis were performed. The dimensions 'Checking' and 'Symmetry and Ordering' were significantly related to dissociative symptomatology. A clear-cut lack of association was found in 'Washing and Cleaning', 'Counting and Touching' and 'Aggressive Impulses and Fantasies'. HZI dimensions significantly discriminated patients with high from patients with low dissociative symptomatology. Psychodynamic and therapeutical aspects of these findings are discussed.

Risk factors for new depressive episodes in primary health care: an international prospective 12-month follow-up study.

BACKGROUND: Studies that examined community samples have reported several risk factors for the development of depressive episodes. The few studies that have been performed on primary care samples were mostly cross-sectional. Most samples had originated from highly developed industrial countries. This is the first study that prospectively investigates the risk factors of depressive episodes in an international primary care sample. METHODS: A stratified primary care sample of initially non-depressed subjects (N = 2,445) from 15 centres from all over the world was examined for the presence or absence of a depressive episode (ICD-10) at the 12 month follow-up assessment. The initial measures addressed sociodemographic variables, psychological/psychiatric problems and social disability. Logistic regression analysis was carried out to determine their relationship with the development of new depressive episodes. RESULTS: At the 12-month follow-up, 44% of primary care patients met ICD-10 criteria for a depressive episode. Logistic regression analysis revealed that the recognition by the general practitioner as a psychiatric case, repeated suicidal thoughts, previous depressive episodes, the number of chronic organic diseases, poor general health, and a full or subthreshold ICD-10 disorder were related to the development of new depressive episodes. CONCLUSIONS: Psychological/psychiatric problems were found to play the most important role in the prediction of depressive episodes while sociodemographic variables were of lower importance. Differences compared with other studies might be due to our prospective design and possibly also to our culturally different sample. Applied stratification procedures, which resulted in a sample at high risk of developing depression, might be a limitation of our study.

Amygdala-hippocampal atrophy and memory performance in dementia of Alzheimer type.

The aim of the present study was to examine the involvement of brain structures, especially the amygdala-hippocampal complex, in dementia of Alzheimer type (DAT), and to assess the relation of amygdala-hippocampal atrophy with memory dysfunction. 14 patients with DAT and 10 healthy age-matched controls were examined with different neuropsychologic tests including the UCLA-Auditory Verbal Learning Test. MRI was performed with a conventional 1.5-tesla scanner. Atrophy was found in many brain structures of demented subjects in comparison with healthy age-matched controls. The volumes of amygdala-hippocampal complexes and of the temporal lobes of demented subjects were more reduced than the total brain volume and other structures. Memory dysfunction was highly correlated with atrophy of the amygdala-hippocampal complexes and of the temporal lobes. Consequently, DAT seems to affect the amygdala-hippocampal complex and their related function (i.e. memory) more than other cerebral structures, but cerebral degeneration in DAT is not restricted to these structures.