Preventing progression to first-episode psychosis in early initial prodromal states.

BACKGROUND: Young people with self-experienced cognitive thought and perception deficits (basic symptoms) may present with an early initial prodromal state (EIPS) of psychosis in which most of the disability and neurobiological deficits of schizophrenia have not yet occurred. AIMS: To investigate the effects of an integrated psychological intervention (IPI), combining individual cognitive-behavioural therapy, group skills training, cognitive remediation and multifamily psychoeducation, on the prevention of psychosis in the EIPS. METHOD: A randomised controlled, multicentre, parallel group trial of 12 months of IPI v. supportive counselling (trial registration number: NCT00204087). Primary outcome was progression to psychosis at 12- and 24-month follow-up. RESULTS: A total of 128 help-seeking out-patients in an EIPS were randomised. Integrated psychological intervention was superior to supportive counselling in preventing progression to psychosis at 12-month follow-up (3.2% v. 16.9%; P = 0.008) and at 24-month follow-up (6.3% v. 20.0%; P = 0.019). CONCLUSIONS: Integrated psychological intervention appears effective in delaying the onset of psychosis over a 24-month time period in people in an EIPS.

The Munich 15-year follow-up study (MUFUSSAD) on first-hospitalized patients with schizophrenic or affective disorders: assessing courses, types and time stability of diagnostic classification.

OBJECTIVE: In the context of the development of DSM-V and ICD-11 it appears to be useful to get further data on the validity of the diagnostic differentiation between schizophrenic and affective disorders. This study investigated the relevance of the main diagnostic groups schizophrenia, schizoaffective psychosis and affective disorder in the context of different diagnostic systems (ICD-9, ICD-10, DSM -IV), assessing their time stability, long-term courses, types and functional outcome. METHODS: A total of 323 first hospitalized inpatients of the Psychiatric Department of the University Munich were recruited at index time. The full follow-up evaluation including standardized assessment procedures could be performed in 197 patients. RESULTS: The re-diagnosis of the patients' disorders shows that with the transition from ICD-9 to ICD-10 or DSM-IV, the group of affective disorders increased numerically while the diagnostic groups of schizophrenia and schizoaffective disorders decreased in size. The structured clinical interview for DSM-IV (SCID) analysis showed that altogether ICD-10 and DSM-IV had a relatively high diagnostic stability. Of the patients with an ICD-10 diagnosis of schizophrenia, 57% had a chronic course; 61% of the patients with a DSM-IV diagnosis of schizophrenia. Patients with affective disorders, according either to ICD-10 or DSM-IV, had in more than 90% of the cases an episodic-remitting course. In terms of prediction of long-term outcome regarding the differentiation between chronic and non-chronic course, the ICD-10 diagnoses did give a slightly better predictive result than a dimensional approach based on the key psychopathological syndrome scores. CONCLUSIONS: The differentiation between schizophrenic and affective disorders seems meaningful especially under predictive aspects. A dimensional syndromatological description does not exceed the predictive power of the investigated main diagnostic categories, but might increase the clinically relevant information.

Time course of antipsychotic treatment response in schizophrenia: results from a naturalistic study in 280 patients.

OBJECTIVE: To describe the course of positive and negative symptoms during inpatient treatment and examine remission and response rates under routine clinical care conditions. METHODS: Two hundred and eighty inpatients with schizophrenia (DSM-IV criteria) were assessed with the Positive and Negative Syndrome Scale (PANSS) at admission and at biweekly intervals until discharge from hospital. Remission was defined according to the symptom-severity component of the consensus criteria (Remission in Schizophrenia Working Group) as a rating of three or less in the relevant PANSS items at discharge, and response as a reduction of at least 20% in the PANSS total score from admission to discharge. RESULTS: The mean duration of inpatient treatment was 54.8 days. Of the total sample, 78.5% achieved the criteria for response and 44.6% those for remission. Mean PANSS total scores decreased from 72.4 at admission to 52.5 at discharge (p<0.001). A reduction in PANSS total scores was found from visit to visit, up to week 8. The most pronounced decline was observed within the first two weeks of treatment. CONCLUSION: Response rates were comparable to those found in efficacy studies, and remission rates were slightly higher. This may be explained by differences in the selection and the treatment of patients. Nevertheless, the findings might indicate that a complex naturalistic treatment approach is beneficial in terms of effectiveness.

Reduced gray matter brain volumes are associated with variants of the serotonin transporter gene in major depression.

The serotonergic system is involved in the pathophysiology of major depression as well as in the early central nervous system development and adult neuroplasticity. The aim of the study was to examine in 77 patients with major depression and 77 healthy controls the association between the triallelic polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) and gray matter (GM) brain volumes measured with 1.5 T magnetic resonance imaging. Voxel-based morphometry were estimated on magnetic resonance images and genotyping was performed. We found that healthy controls have a strong association between the 5-HTTLPR and GM volumes of the dorsolateral prefrontal cortex, left anterior gyrus cinguli, left amygdala as well as right hippocampus, whereas there is no such association in patients with major depression. Healthy subjects carrying the S- or L(G)-allele have smaller GM volumes than those with the L(A)-allele, indicating that 5-HTTLPR contributes to the development of brain structures. Patients with depression show reduced GM volumes, particularly when they are homozygous for the L(A)-allele, suggesting that these patients are more vulnerable for morphological changes during depressive episodes.

Standardized remission criteria in schizophrenia: descriptive validity and comparability with previously used outcome measures.

INTRODUCTION: Standardized consensus criteria for remission in schizophrenia were recently proposed. As yet, the validity of these criteria and their comparability with previously used outcome measures are unclear. METHODS: The symptom-severity component of the proposed remission criteria was applied to 288 inpatients who fulfilled the ICD-10 criteria for schizophrenia. Global functioning and psychopathological symptoms were assessed using GAF, PANSS, SANS, HAM-D and CDSS. RESULTS: When patients with symptom remission at discharge from hospitalization (n=158, 54.9%) were compared to those without symptom remission, significant differences were found with respect to the global functioning (GAF) and all observed psychopathological symptom dimensions. The percentage agreement with previously used outcome measures ranged between 52.6 and 80.0%, the kappa values between 0.120 and 0.594. A moderate accordance (kappa value: 0.495) was found with a Clinical Global Impression (CGI) severity score of three or less. DISCUSSION: The results indicate a high descriptive validity of the symptom-severity component of the proposed remission definition. However, the new criteria differ partially from previously used outcome measures. This aspect should be considered in the interpretation of clinical trials.

Structural brain alterations at different stages of schizophrenia: a voxel-based morphometric study.

Structural alterations in schizophrenia have mainly been regarded as the result of neurodevelopmental processes. However, it remains unresolved whether the pattern of morphological brain changes differs between different stages of disease. We examined structural brain changes in 93 first-episode (FES) and 72 recurrently ill (REZ) patients with schizophrenia (SZ) and 175 matched healthy control subjects (HC) using cross-sectional and conjunctional voxel-based morphometry (VBM) of whole-brain MRI data in a three-step approach. We found significant grey matter density (GMD) reductions in FES compared to HC bilaterally in the temporal and prefrontal areas, including the anterior cingulate gyrus, as well as in both thalami. Hippocampus and amygdala were affected on the left side (P<0.05, corrected). In REZ patients this pattern was spatially extended. The basal ganglia were exclusively reduced in the recurrently ill group compared to controls. Common to both disease groups were reductions in the bilateral perisylvian regions, the opercular region, the insula, prefrontal cortex, left inferior temporal gyrus, limbic system including hippocampus and amygdala, and the thalami. In FES patients there were no regions affected that were not also affected in REZ patients. In contrast, REZ patients showed extended alterations within the frontal and temporal regions, the hippocampus, amygdala and exclusively in the basal ganglia relative to the FES patients. Our findings suggest a system-specific involvement of neuronal networks in schizophrenia. Furthermore, our data suggest that in the advanced stages of schizophrenia additional cortical and subcortical brain areas become involved in the disease process. Longitudinal data will be required to further test this hypothesis.

Structural brain alterations in subjects at high-risk of psychosis: a voxel-based morphometric study.

Forty Untreated high-risk (HR) individuals for psychosis and 75 healthy control subjects (HC) matched for age, gender, handedness and educational level were investigated by structural MRI. HR subjects were recruited at the Early Detection and Intervention Centre for Mental Crises (FETZ) of the Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University, Germany. Measurements of gray matter volumes were performed by voxel-based morphometry using SPM5. The sample of HR subjects showed GM volume reductions in frontal, lateral temporal and medial temporal regions compared to the healthy control group. These regions are compatible with structural findings in the clinically apparent disease of schizophrenia.

Severe mental illness in depression.

OBJECTIVE: The study aimed to evaluate the outcome from in-patient treatment in major depressive disorders (MDD) and its impact on the patients' 1 year outcome under the present routine care conditions. METHOD: The reported data stem from a multicentric follow-up study on the course and outcome of patients with MDD. Patients enrolled in the study had their first or multiple psychiatric hospitalization and fulfilled the ICD-10 criteria for a depressive disorder. During in-patient treatment patients were standardized assessed in 2-weekly intervals, with yearly follow-up evaluations after discharge. RESULTS: The analyses revealed that the elimination of depressive symptoms and a return to premorbid levels of functioning is a rarity in the in-patient treatment of MDD. Moreover, the analyses revealed that the achieved level of response during in-patient treatment clearly determines the patients state 1 year after discharge from in-patient treatment. CONCLUSION: Considering that persisting depressive symptoms are associated with a range of unfavourable outcomes, the present data point to a serious problem in the treatment of MDD and the urgent need to further optimize antidepressive treatment strategies.

Striatal dopamine transporter availability is associated with the productive psychotic state in first episode, drug-naive schizophrenic patients.

OBJECTIVE: Supposing a "hyperdopaminergic State" associated at least with acute psychotic illness phases in schizophrenia, a direct relationship between striatal dopamine metabolism and the core psychopathological symptoms rarely can be provided. Recently, a new SPECT ligand to the presynaptic dopamine transporter (DAT) was introduced. Association of DAT availability and the acute psychotic syndrome is now demonstrated in a large cohort of first episode, never treated schizophrenic patients. METHODS: Twenty-eight inpatients suffering from a first acute exacerbation of schizophrenia and 12 healthy control subjects underwent SPECT scanning with the new radioligand [(99m)Tc]TRODAT-1. On the day of SPECT, psychopathology was assessed using specific scales including PANSS. RESULTS: There was no significant difference in [(99m)Tc]TRODAT-1 specific binding to the striatal DAT comparing both groups. The extend of hallucinations was significantly inversely correlated with DAT availability in patients with a predominantly positive syndrome type. DISCUSSION: Our data support evidence that differences in presynaptic dopaminergic activity in schizophrenic patients are associated with the extend of the acute psychotic syndrome. [(99m)Tc]TRODAT-1 seems to be a useful agent for in vivo assessment of a psychopathological association with dopamine metabolism.

[Diagnostics and therapy of depressive symptoms in schizophrenic patients]. / Bei Schizophreniepatienten immer abklären. Steckt hinter den Negativ-symptomen eine Depression?

The occurrence of depressive symptoms in schizophrenia is fairly common. In contrast to earlier assumptions, they usually have unfavorable consequences on the course of the disease. The response of depressive symptoms to therapy is well documented by empirical evidence and studies. In reality, however, the treatment of depressive symptoms in cases of schizophrenia occurs too rarely. This lack of medical treatment is partially explained by the clinicians' apprehension that antidepressive therapy could provoke a flare up of the psychosis. Nonetheless, this situation is often founded on the incorrect assessment of the depressive symptoms as negative symptoms that, in turn, are regarded by many clinicians as having limited treatability. In regards to this circumstance, a rethinking is desirable and, as a matter of principle, necessary.

[Modern therapy for dementia]. / Alltagskompetenzen erhalten, Wohlbefinden steigern. Das sind die Ziele einer modernen antidementiven Therapie.

The most frequently diagnosed dementia diseases include Alzheimer disease (AD), vascular dementia (VD) and dementia with Lewy bodies. Cholinesterase (ChE) inhibitors and the NMDA receptor antagonist memantine are currently recommended as first line drugs for the treatment of AD. These anti-dementia drugs have not yet been approved for the treatment of VD and DLB although the results of controlled clinical studies support the effectiveness of the ChE inhibitors for both diseases. The treatment of the primary disease and the secondary prevention of cerebrovascular accidents constitute the primary objectives of VD therapy. Although single or multiple domain cognitive deficits are the clinical key symptoms of dementia, noncognitive psychopathological symptoms (so-called behavioral disorders) are particularly common and may even dominate the clinical course in the moderate to severe stages. Therefore, it is important to recognize, diagnose and specifically treat these additional symptoms. During the last decade, the classic neuroleptics and benzodiazepine have been largely replaced by modern antidepressants, atypical antipsychotics and benzodiazepine analogues.

Obsessive-compulsive disorder (OCD) with psychotic symptoms and response to treatment with SSRI.

The co-occurrence of obsessive-compulsive and psychotic symptoms in one patient often represents a diagnostic problem. Distinguishing among a schizophrenic disorder with comorbid obsessional symptoms, an OCD with comorbid psychotic symptoms, or an OCD and schizophrenia or any other psychotic disorder is of clinical importance, since the different diagnoses have different therapeutic as well as prognostic implications. In the following case report we describe a patient who suffered from a typical OCD for more than 18 years and then developed clear psychotic symptoms that completely remitted after treatment with citalopram.

Irritable psychomotor elation in depressed inpatients: a factor validation of mixed depression.

BACKGROUND: Early authors described hypomanic symptoms as mixed features in depressive episode, but this syndrome has not been sufficiently explored in previous studies. METHODS: 958 consecutive depressed patients were assessed by using a standardized method in terms of 43 psychiatric symptoms at hospitalization. RESULTS: A principal component analysis, followed by varimax rotation, extracted six interpretable factors: typical vegetative symptoms, depressive retardation/loss of feeling, hypomanic syndrome, anxiety, psychosis, and depressive mood/hopelessness. The extracted factor structure was relatively stable among several patient groups. There was no evidence that the hypomanic factor was exaggerated by antidepressant pretreatments before hospitalization. Bipolar diagnoses were associated with higher scores on depressive retardation and hypomanic symptoms, and a lower score on anxiety. LIMITATIONS: Psychiatric syndromes and their interrelationships, found in the present study, may be strongly influenced by the rating instrument used. The sample of this study was depressed inpatients. The results should not be generalized for depressed outpatients or epidemiological depressed populations. CONCLUSIONS: Hypomanic symptoms, as characterized by the flight of ideas, racing thought, increased drive, excessive social contact, irritability, and aggression are a salient syndrome in acutely ill depressed patients, lending support to the factor validity of mixed depression. The symptoms may not be related to pretreatments with antidepressants, or comorbidity of substance abuse, suggesting that they reflect various natural phenomenological manifestations of depressive episodes. Anxiety is unlikely to play a major role in the core phenomenological features of mixed depression. Hypomanic symptoms during a depressive episode were more represented in bipolar disorders, which may serve for further clarifications of latent bipolarity in unipolar depression, and prediction of switch into maniform states under biological depression treatments.

Thalamic volume in first-episode and chronic schizophrenic subjects: a volumetric MRI study.

OBJECTIVE: The thalamus, as a composite of several functionally very different nuclei, is a major relay and filter station in the CNS and is significantly involved in information processing and gating. The aim of our study is to investigate first-episode and chronic patients and controls to shed light on the potential pathogenetic role of the thalamus in schizophrenia and to assess the relationship between thalamic volumes and psychopathology ratings. METHODS: Forty-three male right-handed chronic and 25 male right-handed first-episode schizophrenic patients treated at the psychiatric hospital of the Ludwig-Maximilians University in Munich and 50 male control subjects were enrolled into the study. Demographic information and current symptom profile of all schizophrenic subjects were assessed using a semistructured interview, including a variety of measures relevant to the study. Volumetry of the thalamic gray and white matter was obtained with 1.5 T MRI, using the BRAINS software application. RESULTS: No significant differences regarding thalamic volumes were detected across groups. However, negative symptoms were significantly correlated with thalamic volumes in first-episode patients, whereas duration of illness and extrapyramidal symptoms were related to thalamic volumes in chronic patients. SUMMARY: Our findings indicate that, while the thalamus might be involved in the pathogenesis of negative symptoms, thalamic volume reduction is not a required element in the pathophysiology of the schizophrenic phenotype.

[Schizophrenics in the doctor's office. Diagnostic and therapeutic aspects]. / Schizophrene Patienten in der Allgemeinarztpraxis. Checkliste hilft bei der Früherkennung.

The diagnosis and treatment of schizophrenia is usually an interdisciplinary affair, with particular stress on cooperation between family doctor and psychiatrist. The practicing physician has a major role to play in the recognition of early schizophrenia. For reasons of time and the fact that further specialist diagnostic measures are mostly required, he will, as a rule, have to restrict himself to screening examinations. Patients with a positive screening outcome will be referred to a specialized early-recognition center or a specialist clinic for further diagnostic clarification. But the family doctor also has an important role in the treatment of these patients, e.g. when physical comorbidity presents, the patient rejects treatment by a psychiatrist, or has an early form of schizophrenia or a relapse. Today, medical treatment employs atypical neuroleptics, and treatment should be initiated as early as possible.

[The classification of functional psychoses: the impact of ICD-10 diagnoses (research diagnostic criteria) for the prediction of the long-term course]. / Klassifikation der funktionellen Psychosen: Die Bedeutung der ICD-10-Diagnosen (Forschungskriterien) für die Vorhersage des Langzeitverlaufes.

One major objective of Emil Kraepelin's system of the functional psychoses was to establish a prognostically relevant diagnostic classification. Following this idea, 197 first admitted inpatients from the years 1980 - 1982 were examined 15 years later in order to determine the impact of ICD-10 diagnoses (derived from first hospitalisation) for the long-term course. The long-term course was divided into the three course types single episode, episodic-remitting course and chronic course. The results showed that 57 % of the patients with schizophrenia, 50 % of the patients with persistent delusional disorders, 20 % of the patients with acute and transient psychotic disorders, 10 % of the patients with schizoaffective disorders and only 3 % of those with affective disorders developed a chronic course type. Using a logistic regression analysis, the predictive validity of the ICD-10 diagnoses was compared with those of a dimensional model based on psychopathological and demographic data. The results revealed that the predictive validity of the dimensional model (77 %) does not exceed the predictive validity of ICD-10 diagnoses (78 %).

Fifteen-year follow-up of ICD-10 schizoaffective disorders compared with schizophrenia and affective disorders.

OBJECTIVE: The nosological status of schizoaffective disorders is still unclear. The aim of the present study was to compare ICD-10 schizoaffective disorders to schizophrenia and affective disorders with respect to the clinical picture and the long-term outcome. METHOD: Two hundred and forty-one first-admitted inpatients from the years 1980-1982 who fulfilled the ICD-10 criteria for schizophrenia, schizoaffective or affective disorders were included. Patients were examined at the time of first hospitalization and then followed-up after 15 years. RESULTS: With respect to the clinical picture at the time of first hospitalization ICD-10 schizoaffective disorders were distinguishable from both schizophrenia and affective disorders. However, with respect to the long-term outcome ICD-10 schizoaffective disorders had a prognosis similar to that of affective disorders. CONCLUSION: Differing prognosis implies that schizoaffective disorders should be distinguished from schizophrenia and suggests their subcategorization under affective disorders.

[Diagnostic shifts of functional psychoses in the transition from ICD-9 to ICD-10]. / Diagnoseverschiebungen der funktionellen Psychosen beim Ubergang von der ICD-9 zur ICD-10.

In order to identify diagnostic changes caused by the transition from ICD-9 to ICD-10, in a sample of 218 first hospitalised patients from the years 1980 and 1981, ICD-9 diagnoses were compared with ICD-10 diagnoses. For this comparison, functional psychoses were classified into five main diagnostic groups. Results showed a decreased frequency of the diagnostic groups schizophrenia, schizoaffective psychoses, and paranoid psychoses and an increased frequency of the diagnostic groups acute psychoses and affective psychoses. With the exception of acute psychoses and schizoaffective psychoses, a high agreement between ICD-9 and ICD-10 diagnoses was found, and the Kappa value was 0.70. With regard to the homogeneity of psychopathological symptoms, ICD-10 diagnoses showed no improvement over ICD-9 diagnoses. Nevertheless, ICD-10 diagnoses have gained in predictive validity because schizophrenia was further narrowed to cases with a more unfavourable outcome.

[Negative symptoms of schizophrenic patients from the perspective of psychiatrists, patients themselves and their relatives]. / Negative Symptome schizophrener Patienten aus der Perspektive der Psychiater, der Patienten selbst und deren Angehörigen.

Clinical experience shows that negative symptoms are affected by environmental factors. Thus, different assessors with different information about patient behavior in different environments may come to different findings of negative symptoms. In this regard, the present study evaluates to what extent the assessment of negative symptoms by schizophrenic inpatients and their relatives compares to interview-based assessments by experts. Therefore, 33 schizophrenic patients were rated by patients themselves, their relatives, and psychiatrists. Negative symptoms were assessed with comparable assessment scales using the modified version of the Scale for the Assessment of Negative Symptoms (SANS) for patients or relatives and the original SANS for psychiatrists. Analyses revealed that the total SANS summary scores as rated by patients and relatives were comparable to scores rated by psychiatrists. Scores on SANS subscales of "alogia" and "attention deficits" differed significantly among the three ratings, while psychiatrists rated the patients' impairments as lower than did the patients themselves or their relatives. These findings indicate that patients' and relatives' ratings could be used to reduce information variance and improve the validity of interview-based, assessed negative symptoms.

Long-term inter-episode stability of syndromes underlying mania.

OBJECTIVE: To explore the stability of diverse manic presentations across manic recurrences. METHOD: A total of 253 bipolar patients who experienced two or more hospitalizations, because of consecutive manic (or mixed) episodes, during a 20-year period were included. All patients had second hospitalizations with an mean interval of 773 days, while 126 and 91 patients had third and fourth hospitalizations with mean intervals of 1559 and 2237 days from the index hospitalization, respectively. Seven symptom scores, previously factor-validated, were calculated. RESULTS: Depressive mood, irritable aggression, psychomotor/thought inhibition, mania, emotional lability/agitation and psychosis were moderately correlated across the index and subsequent hospitalizations. CONCLUSION: A majority of diverse manic presentations were stable across manic recurrences. The stability was not restricted to two consecutive recurrences but appeared widespread over the long-term course of bipolar disorder. The finding may serve for the development of more effective long-term treatment strategies and a clinically more reasonable subtyping of mania.