Standard auditory evoked potentials (AEP) were recorded in 50 schizophrenic patients and 47 normal controls. All patients were rated on the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Negative Symptoms (SANS), the Scale for the Assessment of Positive Symptoms (SAPS), and the Positive and Negative Syndrome Scale (PANSS), and were classified in three groups (positive-type [n = 10], negative-type [n = 23]and mixed-type [n = 17]patients) according to the normative criteria suggested by Kay. The mean latencies of AEP components (N1, P2, N2) and mean peak-to-peak amplitudes (N1P2, P2N2) did not correlate with age, duration of illness, length of hospitalisation or neuroleptic dosage. The evoked response did not differ between the three groups of patients (positive, negative and mixed). There was only a trend (P = 0.075) to a longer N1 latency in the negative-type group and a shorter one in the positive-type group than in the mixed-type and the control groups. The latency of N1 component correlated significantly with negative symptoms of schizophrenia (SANS scores). This correlation was related to the severity of a depressive dimension of the disorder reflected by the “depressive factor” of BPRS or “affective flattening” and “avolition” subscales of SANS.

The Mini International Neuropsychiatric Interview (MINI) is a short diagnostic structured interview (DSI) developed in France and the United States to explore 17 disorders according to Diagnostic and Statistical Manual (DSM)-III-R diagnostic criteria. It is fully structured to allow administration by non-specialized interviewers. In order to keep it short it focuses on the existence of current disorders. For each disorder, one or two screening questions rule out the diagnosis when answered negatively. Probes for severity, disability or medically explained symptoms are not explored symptom-by-symptom. Two joint papers present the inter-rater and test-retest reliability of the MINI the validity versus the Composite International Diagnostic Interview (CIDI) (this paper) and the Structured Clinical Interview for DSM-III-R patients (SCID) (joint paper). Three-hundred and forty-six patients (296 psychiatric and 50 non-psychiatric) were administered the MINI and the CIDI ‘gold standard’. Forty two were interviewed by two investigators and 42 interviewed subsequently within two days. Interviewers were trained to use both instruments. The mean duration of the interview was 21 min with the MINI and 92 for corresponding sections of the CIDI. Kappa coefficient, sensitivity and specificity were good or very good for all diagnoses with the exception of generalized anxiety disorder (GAD) (kappa = 0.36), agoraphobia (sensitivity = 0.59) and bulimia (kappa = 0.53). Interrater and test-retest reliability were good. The main reasons for discrepancies were identified. The MINI provided reliable DSM-III-R diagnoses within a short time frame, The study permitted improvements in the formulations for GAD and agoraphobia in the current DSM-IV version of the MINI.

The purpose of this study was to investigate the relationship of social anxiety and insulin-dependent diabetes mellitus (n = 40 girls between 13 and 19 years of age). Mean duration of diabetes was 7 years. We supposed that this chronic illness may provoke feelings of friendlessness and sadness, social withdrawal and fear of social situations because diabetes entails a series of demands which differentiate the diabetic child from healthy children. Our population was compared with 35 healthy young girls. All were administered the Schedule for Affective Disorders and Schizophrenia for School-Age-Children and completed the State Trait Anxiety Inventory for Children, the Self-Consciousness Scale and the Imaginary Audience Scale. Diagnoses of anxiety disorders across DSM-IIIR do not show significant differences between groups. In self-report inventories, our findings do not support the hypothesis that social anxiety is a pathological symptom in diabetic subjects. However, they were more depressed than the control group. Furthermore, social functioning of the diabetic group did not differ from that of the control group. They were more concerned with their illness than with social anxiety.

Various historical aspects of resistant schizophrenia are described: limitations of treatment efficacy, attempts at proposing therapeutic strategies in non-responding patients, first attempts to define resistance in schizophrenia, and first attempts to distinguish resistance factors. Interest in treatment-refractory schizophrenia was stimulated by several studies in the period 1985–1990, including a pivotal study of clozapine. The need to include biological and psychosocial factors when defining resistance was emphasised by a group who defined a systematic approach to treatment resistance in schizophrenia, including degrees of resistance. The concept of a continuum from full remission to complete refractoriness was proposed by an international study group in 1990. Difficulties in identifying patients with refractory schizophrenia include: variability of schizophrenia diagnostic criteria, lack of consensus concerning good treatment practice with neuroleptic agents, and confusion between resistance, chronicity and severity. A better definition of refractoriness is needed, not only for pharmacological studies but also for a more precise characterisation of a possible subgroup of schizophrenia termed ‘Kraepelinian’.

Previous studies have shown that schizophrenic patients are more likely to be born in winter or early spring months than the general population. Data on 4,207 patients with a hospital diagnosis of schizophrenia were obtained from a mailed survey to public departments of adult psychiatry in metropolitan France. For each year from 1900 to 1965, the expected monthly number of schizophrenic births was calculated and any seasonal variation of live births in the general population was taken into account. Cumulative distributions of the observed and expected number of schizophrenic births were compared using a Kolmogorov-Smirnov type statistic. The seasonal distribution of schizophrenic births was significantly different from that of the general population (P < 0.01). An excess of schizophrenic births was found in the first half of the year, with a peak in April (+ 13%).

The efficacy of zolpidem, a non benzodiazepine hypnotic agent with a short elimination half life, was reviewed, analysing more than 50 international clinical trials published since 1986. The hypnotic activity of zolpidem has been explored in different patient populations including normal volunteers, general practice outpatients and psychiatric out- or in-patients with varying sleep disorders; both transient and chronic. Assessment methods used have included objective and subjective measures of hypnotic efficacy for different treatment durations, with results confirming that 10 mg is superior to placebo. Zolpidem was shown to be superior in most trials on sleep parameters such as total sleep time, sleep onset latency and nocturnal awakenings, but total REM sleep and REM latency were usually unmodified. Zolpidem maintained normal sleep physiology as demonstrated by the preservation of slow wave stages and no, or minimal, effects on sleep architecture after abrupt discontinuation. Consequently, 10 mg is the recommended dose for the short-term treatment of insomnia in the non-elderly; in elderly patients 5 mg has been shown to be effective at inducing sleep whilst giving an optimum safety profile.

In this study, we investigated the prevalence of full syndrome (FS), partial syndrome (PS) and subclinical syndrome (SCS) eating disorders in a sample of 356 high school girls. We identified two cases of anorexia nervosa (0.56%), 14 of bulimia nervosa (3.94%) and one of binge eating disorder (0.28%) according to Diagnostic and Statistical Manual (DSM)-IV. Moreover, 17 girls (4.77%) were recognized as PS cases and 49 (13.7%) as SCS cases. A follow-up is now ongoing to explore the clinical evolution of partial and subclinical syndromes.

The benefits of an antidepressant with an early or rapid onset of action include a more rapid resolution of the debilitating symptoms of depression, a potential reduction in the risk of suicide and cost savings associated with a reduction in hospitalization. While these benefits are valuable, this promise has yet to be fulfilled by any antidepressant. Venlafaxine is a unique serotonin-noradrenaline reuptake inhibitor (SNRI) which produces rapid and prolonged desensitization of β-adrenergic receptors in preclinical studies after both acute and chronic administration of venlafaxine. Results from placebo-controlled and active comparator clinical studies provide evidence that venlafaxine may have an early onset of activity which is most apparent at higher dosages. The early onset is most apparent with rapid escalation of the venlafaxine dosage, and the incidence, therefore, of side effects tends to be higher early after initiating therapy with venlafaxine. Thus, venlafaxine may fill the long awaited need for an antidepressant with an early onset of action.

The potential effects of zolpidem, a non-benzodiazepine hypnotic, on cognitive and psychomotor functions have been explored in more than 30 placebo controlled studies, and in many cases in comparison with benzodiazepine reference hypnotics (ie flunitrazepam, nitrazepam, triazolam). Daytime impact of drug administration on alertness has been studied with the Multiple Sleep Latency Test, and no significant clinical impairment has been found after zolpidem 5 to 10 mg, unlike benzodiazepines. Evaluation of the effects of zolpidem on attention and psychomotor skills (critical flicker fusion threshold, substitution or copying tests, choice reaction times or driving tests, etc) indicate that zolpidem at recommended doses (5 mg in elderly and 10 mg in adults) is unlikely to produce significant detrimental residual effects on daytime vigilance, concentration and coordination performances on the morning after intake. In accordance with its pharmacokinetic and pharmacodynamic properties, the effects on zolpidem on memory functions were limited to the first hours after administration and no significant difference was observed between zolpidem (5–10 mg) and placebo 6 hours after administration; longer memory impairment was observed with flunitrazepam or triazolam. Various groups of subjects were included in these studies, both young adults and elderly subjects, healthy volunteers and insomniac patients, and duration of treatment varied between one single dose and 28 days of repeated intake. In conclusion, experimental evidence demonstrates a satisfactory safety profile of zolpidem (5–10 mg) on daytime cognitive functions as compared to other hypnotics.

The Frankfurt Complaint Questionnaire (FCQ) is a widely used method to investigate non-psychotic subjective experiences of schizophrenics. Less is known about its dimensional structure. Therefore, principal components analyses (PCA) were conducted with the FCQ data of 505 schizophrenics and 187 alcoholics. Furthermore, results of a former analysis using item-to-item comparisons between schizophrenics and alcoholics were examined. PCA yielded two factors called ‘dysphoric concomitants of severe illness particularly impairing concentration’ and ‘subjective experiences of perceptual uncertainties’. Neither of the factors was specific to schizophrenia. The item comparisons suggest that only a group of eight FCQ items (subscale ‘FCQ-S’) is specific to schizophrenia while ten items (‘FCQ-A’) are related more to alcoholism. The validity of FCQ-S and FCQ-A was confirmed: schizophrenics reached high scores in FCQ-S and low scores in FCQ-A; alcoholics scored high in FCQ-A and low in FCQ-S; schizophrenics with an additional alcohol disorder scored high in both of the subscales. It is concluded that direct group comparisons seem to be promising for the identification of non-psychotic subjective phenomena which are characteristic for schizophrenia.

The onset of action of antidepressant drugs was investigated on the basis of two independent multicenter, double-blind efficacy studies comparing amitriptyline (n = 120), oxaprotiline (n = 120), imipramine (n = 506) and moclobemide (n = 580) with placebo (n = 189 + 191). The samples consisted of in- and outpatients diagnosed, according to Diagnostic and Statistical Manual (DSM)-III criteria, as suffering from major depressive disorder. Measures of efficacy criteria were the Hamilton Rating Scale for Depression (HAM-D), the Hamilton Rating Scale for Anxiety (HAM-A) and the Zung Self-Rating Depression scale. By using the Sustained Relative Improvement (SRI) criterion, onset of action was determined in each individual patient as that time point in the 30 day observation period at which a 20% baseline score reduction was achieved without subsequent deterioration. Analogously, a response to treatment was defined as a 50% baseline score reduction. As expected, highly significant differences between active drugs and placebo were found with respect to the total number of improvers and responders. Significant differences between treatment modalities surfaced in the percentage rate as well as the time distribution of premature withdrawals. Yet, unexpectedly, among improvers, the time spans to onset of improvement were found to be independent of treatment modality as indicated by virtually identical cumulative percentages of improvers throughout the whole observation period. The picture was essentially the same for the HAM-A and Zung assessments, except for a significant time lag between observer- and self-ratings. In particular, our analyses revealed no evidence for a delayed onset of action under various antidepressants with large biochemical and pharmacological differences in comparison to placebo. Moreover, the early onset of improvement was highly predictive of later outcome: on average, 70% of the patients showing improvement within the first 14 days became responders. Applying survival-analytical methods, we found that differences between active treatments and placebo emerged within the first 5 days and reached a point of maximum distinction around day 14. After this time point, differences between treatment modalities remained constant until the end of the observation period. According to our data, 20–25% of the patients were, on average, ‘true’ drug responders, thus suggesting that the therapeutic qualities of antidepressants do not lie in the suppression of symptoms, but rather are related to their ability to elicit and maintain certain conditions which allow recovery in a subgroup of patients who would otherwise remain non-responders.

Treatment-resistant schizophrenia does not exist as a discrete entity, so separating patients who will fail to respond to traditional antipsychotics from those who will respond is impossible with 100% accuracy. However, several predictors of poor clinical outcome have emerged from recent research and knowledge of the processes that lead to poor outcome has become increasingly important with the advent of atypical antipsychotics that may be used in patients with treatment-resistant illness. Much of the variation in outcome can be understood in terms of differences in sample selection, outcome definition and stringency of the diagnostic criteria used. Failure to appreciate these mechanisms may lead to over- or underestimation of the proportion of patients with poor treatment response in clinical and research settings. The importance of factors that predict poor outcome should be judged in terms of their effect size and the degree to which alternative explanations for the association with outcome have been excluded. Although much current research is being focused on specific biological predictors, baseline demographic and illness-related factors, such as ethnic group, sex, social class, type of onset, age of onset and concurrent misuse of alcohol or drugs, have large effects on outcome. Although duration of untreated psychosis before first contact with services may independently predict poor outcome, confounding by variables that are associated with both pathways to care and clinical outcome has not been excluded.

Diagnosis of post-stroke depression (PSD) is extremely difficult due to concomitant focal cognitive disturbances or generalized intellectual impairment, and, in some cases, dissociation of mood and affective behavior. The diagnosis has been standardized on the basis of psychiatric criteria in the Diagnostic and Statistical Manual (DSM)-III, an approach that has been criticized for taking into account non-specific stroke-related somatic symptoms. Yet evaluation of the PSD diagnosis by comparing the severity of depressive symptoms in stroke to an age-matched population sample and by conducting a controlled antidepressant treatment study in unselected PSD patients has failed to disclose any evidence that non-specific symptoms influence the diagnosis of PSD. The prognosis, however, of early vs late diagnosed PSD and the response to treatment of early vs late diagnosed PSD differ, indicating that PSD diagnosed according to DSM-III criteria covers a heterogeneous group of etiologically different conditions.

Anxiety and depression are often interlinked as demonstrated by clinical, epidemiological, psychopharmacological and even genetic studies. However, robust biochemical and electrophysiological evidence for linkage or separation of mood and anxiety disorders is scarce. Brain stem auditory evoked potentials (BASEP) can easily and non-invasivly be measured in psychiatric patients and reflect neurophysiological processes in the brain stem. The aim of the present study was to evaluate BASEP in drug-free patients suffering from panic disorder or major depression and to compare these to healthy controls. Patients (n = 26; panic = 16, depression = 10) were diagnosed according to Diagnostic and Statistical Manual (DSM)-III-R criteria assessed by the Hamilton Anxiety and Hamilton Depression Scales, and all underwent 3 weeks of medications washout. All subjects (n = 36) completed the study. N3 latency was decreased in the patient group (P < 0.05), N3-5 interval was lengthened (P < 0.05), the N3 latency correlated with anxiety scores and depression scores correlated with the N3 and N5 latency periods. In conclusion, our small sample demonstrated shared electrophysiological variables in panic disorder and depression, further supporting the concept of spectrum disorder.

The present article reviews the recent molecular genetic findings in affective disorders. Results of linkage and association studies are discussed in regard to the main limitations of these approaches in psychiatric disorders. On the whole, linkage and association studies contributed to the localisation of some potential vulnerability genes for Bipolar affective disorder on chromosomes 18, 5, 11, 4, 21 and X. The hypothesis of anticipation in affective disorders is also considered in light of interesting results with trinucleotide repeat mutations.

Review of geographical comparisons of the prevalence of schizophrenic disorders found a ten-fold range difference between geographical contiguous groups, with high and low prevalence pockets. We performed a 1-year prevalence study of schizophrenia in a limited area of Reunion Island in the Indian Ocean, and analysed the prevalence variability in contiguous regions of this area. We found one of the highest reported age-corrected (above 15 years) 1-year prevalence of schizophrenia (14.9 per thousand). Large discrepancies in the distribution of prevalence rates of schizophrenia were observed between the five towns analysed. Interestingly, when a higher prevalence was observed, it was highly correlated with an increase of the percentage of familial cases (r = 0.989, df = 3, P = 0.0014). Presence of founder effect often described in geographical isolates could explain the high prevalence rate and the heterogeneity between towns observed in our sample.

Probably in association with changes in the economic structure and high unemployment rates in western industrialized countries, homelessness is becoming more apparent publicly and receiving increased media attention. More studies on the issue of mental illness and homelessness have been performed in recent years in North America while hardly any representative and reliable data exists concerning Germany and some other European countries. The aim of our study was 1) to assess alcohol abuse and dependency as well as other mental disorders in a representative sample of homeless men in Munich using reliable methods of case identification (Diagnostic Interview Schedule [DIS and DIS/DSM-III diagnoses); 2) to compare homeless alcoholics with homeless non-alcoholics in our sample on relevant variables and issues and 3) to compare our data from the sample of homeless men in Munich with data obtained by others using the same case identification procedure (DIS/DSM-III diagnoses). According to our results, the lifetime prevalence of any DIS/DSM-III Axis I diagnoses was 94.5% and the lifetime prevalence of substance use disorder was 91.8%. The single most prevalent diagnosis among homeless males in Munich was alcohol dependency (lifetime 82.9%), while alcohol abuse (lifetime 8.2%) and drug abuse/dependency were considerably lower (lifetime 17.8%). Data show that alcoholism and its consequences were more severe in the Munich as compared to the Los Angeles homeless sample. Homeless alcoholics showed a high comorbidity with other mental disorders (lifetime) such as affective disorders (44.4%), anxiety disorders (22.6%), drug abuse/dependence (18.8%) and schizophrenia (12.0%); 64% of those with alcoholism at some time during their life had at least one other lifetime mental disorder. Alcohol-related patterns of living and symptoms as well as social or role functioning are described for homeless alcoholics in Munich and compared with data from other relevant studies. Considering the extremely high prevalence of alcohol dependence frequently in combination with other mental disorders, the use of alcohol rehabilitation and other services as well as self-help groups was minimum among Munich homeless alcoholics. New concepts to deal with these problems are needed and if they exist, they need to be implemented.

Cortisol-binding globulin (CBG) is an alpha-1-glycoprotein with high affinity for cortiso that could be a potential biological marker of chronic stress, according to several previous studies. In order to examine CBG concentrations in bipolar disorder, we determined serum CBG levels by radioimmunoassay with monoclonal antibodies in a sample of 39 RDC bipolar I patients in remission and 21 healthy age-, sex- and weight-matched control subjects. Only lithium treatment was permitted. Plasma cortisol and serum lithium levels were also determined. Bipolar males showed statistically significant lower serum CBG levels than controls, whereas women showed very similar values. No correlation was found between CBG levels and cortisol or lithium concentrations. It is concluded that CBG levels are affected by chronic affective illness, even during remission periods, at least in bipolar males.

The Mini International Neuropsychiatric Interview (MINI) is a short diagnostic structured interview, developed in clinician (MINI-CR) and patient-rated (MINI-PR) formats, for 17 Diagnostic and Statistical Manual (DSM)-III-R Axis I psychiatric disorders. This study, which investigates the validity of the MINI in relation to the Structured Clinical Interview for DSM-III-R Patients (SCID-P), was conducted in conjunction with a similar study, investigating the validity of the MINI in relation to the Composite International Diagnostic Interview (CIDI) for International Statistical Classification of Disease (ICD)-10. Both studies also examined the inter-rater and test-retest reliability of the MINI. Three hundred and seventy subjects (330 in Florida and 40 in Paris) participated in the validation of the MINI versus the SCID-P. Of these, 308 had at least one psychiatric disorder and 62 were non-patient adult controls. Eighty of the subjects (40 in Florida and 40 in Paris) also participated in the parallel study of the validity of the MINI versus the CIDI. The 330 Florida subjects first completed the patient-rated version of the MINI. All subjects were administered the MINI-CR (after the MINI-PR in the case of the Florida subjects), followed by the SCID-P. The MINI-CR was rated by two interviewers for 42 subjects in Florida and 42 in Paris (inter-rater reliability test) and readministered by a third blind interviewer one to two days after the initial rating (test-retest reliability test). Overall, the results supported the validity and reliability of the MINI. In addition, administration of the MINI-CR took half as long as administration of corresponding sections of the SCID-P. The application of short structured interviews in clinical and research settings is discussed.

A prospective study in treatment-resistant schizophrenic patients was performed over 10 years to evaluate the therapeutic response to clozapine and the variables related to this treatment. Eighty schizophrenic and schizoaffective patients (according to Diagnostic and Statistical Manual [DSM]-IIIR criteria), considered as refractory (previously resistant to at least two different typical neuroleptics), were studied. The average dose of clozapine was 267 mg/d. The clinical variables considered were: Brief Psychiatric Rating Scale (BPRS), number of admissions before and after clozapine treatment and the Strauss-Carpenter scale as measures of efficacy; Premorbid Adjustment Scale (PAS), to assess personal and social adjustment before illness; Karolinska Personality Scale (KPS) to assess stable traits of personality; and the Simpson-Angus scale as a measure of extrapyramidal symptoms. Sixty percent of patients showed a significant improvement after clozapine treatment. Side-effects were mild and well tolerated, with no cases of haematological disturbance and only five withdrawals because of adverse events. The severity of the episode, according to BPRS score and anxiety as a personal trait, are related to good prognosis. Other relationships between improvement and clinical and demographic variables are discussed.