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Psychoneuroendocrinology. 2008 May;33(4):507-16. Epub 2008 Mar 14.
Testosterone and gonadotropins but not estrogen associated with spatial ability in women suffering from schizophrenia: a double-blind, placebo-controlled study.
Bergemann N, Parzer P, Kaiser D, Maier-Braunleder S, Mundt C, Klier C.
Biological psychiatry, 2007, 61(4): 551-3
Omega-3 fatty acids supplementation in children with autism: a double-blind randomized, placebo-controlled pilot study
G. P. Amminger, G. E. Berger, M. R. Schafer, C. Klier, M. H. Friedrich and M. Feucht
BACKGROUND: There is increasing evidence that fatty acid deficiencies or imbalances may contribute to childhood neurodevelopmental disorders. METHODS: We conducted a randomized, double-blind, placebo-controlled 6-week pilot trial investigating the effects of 1.5 g/d of omega-3 fatty acids (.84 g/d eicosapentaenoic acid, .7 g/d docosahexaenoic acid) supplementation in 13 children (aged 5 to 17 years) with autistic disorders accompanied by severe tantrums, aggression, or self-injurious behavior. The outcome measure was the Aberrant Behavior Checklist (ABC) at 6 weeks. RESULTS: We observed an advantage of omega-3 fatty acids compared with placebo for hyperactivity and stereotypy, each with a large effect size. Repeated-measures ANOVA indicated a trend toward superiority of omega-3 fatty acids over placebo for hyperactivity. No clinically relevant adverse effects were elicited in either group. CONCLUSIONS: The results of this study provide preliminary evidence that omega-3 fatty acids may be an effective treatment for children with autism.
Biological psychiatry, 2007, 61(10): 1215-7
BACKGROUND: While there is evidence that some cases of schizophrenia may be associated with microbial infections, the role of microbial agents has not been investigated in people with emerging psychosis. METHODS: Participants were 105 help seeking ultra-high risk individuals. Psychiatric measures included the Brief Psychiatric Rating Scale and the Scale for the Assessment of Negative Symptoms. Serum IgG antibodies against human herpesviruses and Toxoplasma gondii were determined using immunoassay methods. Multiple linear regression with adjustment for age and sex was applied to test associations between serum antibodies and psychiatric measures. RESULTS: Higher levels of serum IgG antibodies against Toxoplasma gondii in Toxoplasma-positive individuals were significantly associated with more severe positive psychotic symptoms. No significant association was observed between antibody levels and psychiatric measures in individuals positive for human herpesviruses. CONCLUSIONS: In some individuals infection with Toxoplasma gondii may be an environmental factor contributing to the manifestation of positive psychotic symptoms.
Curr Opin Psychiatry, 2007, 20(4): 359-364
PURPOSE OF REVIEW: The aim of this article is to review recent epidemiological research on age-of-onset of mental disorders, focusing on the WHO World Mental Health surveys. RECENT FINDINGS: Median and inter-quartile range (IQR; 25th-75th percentiles) of age-of-onset is much earlier for phobias (7-14, IQR 4-20) and impulse-control disorders (7-15; IQR 4-35) than other anxiety disorders (25-53, IQR 15-75), mood disorders (25-45, IQR 17-65), and substance disorders (18-29, IQR 16-43). Although less data exist for nonaffective psychosis, available evidence suggests that median age-of-onset is in the range late teens through early 20s. Roughly half of all lifetime mental disorders in most studies start by the mid-teens and three quarters by the mid-20s. Later onsets are mostly secondary conditions. Severe disorders are typically preceded by less severe disorders that are seldom brought to clinical attention. SUMMARY: First onset of mental disorders usually occur in childhood or adolescence, although treatment typically does not occur until a number of years later. Although interventions with early incipient disorders might help reduce severity-persistence of primary disorders and prevent secondary disorders, additional research is needed on appropriate treatments for early incipient cases and on long-term evaluation of the effects of early intervention on secondary prevention.
Neuropsychiatr, 2007, 21(1): 37-44
Over the last decade there has been considerable interest in early intervention in schizophrenia and other psychotic disorders, driven by observations that early intervention might favorably alter the course of illness. New clinical and research programs have been established around the globe aiming to reduce treatment delays in psychosis and, more recently, to identify and possibly treat individuals in the pre-psychotic phase who are at imminent risk of developing psychosis. Since May 2004, a service for individuals at high risk (HR) for psychosis has been established at Vienna General Hospital. Individuals are offered comprehensive assessment and treatment which includes participation in a RCT investigating the effects of Omega-3 fatty acids versus placebo in addition to standard care. The aim of this article is to describe (1) classification of psychotic symptoms in incipient psychosis and (2) findings of the screening process as well as baseline characteristics in individuals with and without transition to psychosis. Inclusion Criteria: 1. Age 13 to 24 years 2. High Risk (HR) as classified by Yung et al. (1998) HR criteria: one or more of following characteristics occurred within the last 12 months: 1. Frank psychotic symptoms < 1 week 2. Attenuated psychotic symptoms > 1 week, several times per week 3. Drop in GAF of > 30% (>1 months) plus family history of psychosis or individual has schizotypal personality disorder Other psychiatric measures: SCID for DSM-IV, PANSS, MADRS, and the UKU side effect rating scale. Between May 2004 and June 2005, 140 individuals were referred to our service for suspected psychosis. 69 individuals (49,3%) met HR criteria, 21 (15%) were detected with first-episode psychosis at initial presentation; 50 (35,7%) individuals did not meet criteria for HR or DSM-IV psychotic disorder. 42 (60,9%) of 69 individuals with HR agreed to participate in the proposed EPA/DHA treatment trial. Co-morbidity of axis-I disorders was high in the HR group: 54,3% affective disorders, 40% anxiety/obsessive-compulsive disorders, 14,3 substance related disorders, 11,4% eating disorders and 2,9% somatoform disorders. To date 6 (14,3%) individuals have made a transition to psychotic disorder. These subjects scored significantly higher at the negative and at the general psychopathology scale ofPANSS and at the MADRS at time of randomization. Early detection and intervention in psychotic disorders seems to be a feasible goal which can be achieved in an outpatient setting. Individuals with HR can be detected and already show a substantial loss of functioning. In the process of screening for individuals with HR a high number of undiscovered cases of psychosis can be found. Given their high prevalence, treatment of comorbid axis-I conditions should be carefully addressed in HR and studied in relation to the risk of progression to psychosis. In contrast to antipsychotics, Omega-3 fatty acids have a high acceptance among youth and parents. At this stage the role of Omega-3 fatty acids remains unclear because the trial is not finished yet.
Acta-Psychiatr-Scand. 2006 Nov; 114(5): 337-45 Treated incidence of first-episode psychosis in the catchment area of EPPIC between 1997 and 2000.
Amminger,-G-P; Harris,-M-G; Conus,-P; Lambert,-M; Elkins,-K-S; Yuen,-H-P; McGorry,-P-D
Objective: To identify the treated incidence of psychosis in catchment of the Early Psychosis Prevention and Intervention Centre (EPPIC), Melbourne, Australia. Method: Cases were aged 15-29 years with a first episode of a psychotic disorder accepted into EPPIC between 1997 and 2000. Age- and sex-specific incidence rates per 10 000 person-years were calculated in 5 year age bands. Rate ratios were used for age group comparisons. Results: The age-specific treated incidence of first-episode psychosis in 15-29-year old individuals was 16.7 per 10 000 person-years in males, and 8.1 per 10 000 person-years in females. The incidence was highest in 20-24-year-old males and in 15-19-year-old females. For both sexes, incidence rates were significantly lower in the 25-29-year age group. Conclusions: The incidence of psychosis in the catchment of EPPIC was higher than previously reported, especially in female teenagers. Peak rates in 15-24 year olds suggest a youth model approach to early psychosis may be indicated.
Int-Rev-Psychiatry. 2006 Apr; 18(2): 85-98 Bioactive lipids in schizophrenia. Berger,-G-E; Smesny,-S; Amminger,-G-PBioactive lipids, in particular arachidonic acid (AA), are vital for monoaminergic neurotransmission, brain development and synaptic plasticity. Phospholipases A2 (PLA2) are key-enzymes in AA metabolism and are activated during monoaminergic neurotransmission. Reduced membrane AA levels, and an altered activity of PLA2 have been found in peripheral membranes of drug-naive patients with schizophrenia with some conflicting results in more chronic patient populations. Furthermore, in vivo brain phosphorus-31 magnetic resonance spectroscopy suggests reduced lipid membrane precursors (phosphomonoesters) and increased membrane breakdown products (phosphodiesters) in drug-naive or early treated first-episode schizophrenia patients compared to age-matched controls or chronic populations and these changes were correlated with peripheral red blood cell membrane AA levels. We postulate that processes modulating membrane lipid metabolism are associated with psychotic illnesses and might partially explain the mechanism of action of antipsychotic agents, as well as experimental agents such as purified ethyl-eicosapentaenoic acid (E-EPA). Recent supplementation trials suggest that E-EPA is a modestly effective augmentation treatment resulting in reduced doses of antipsychotic medication in acutely ill patients with schizophrenia (but not in residual-type schizophrenia). This review investigates the role of bioactive lipids in schizophrenia and its treatment, as well as its potential use in prevention..
Early-onset of symptoms predicts conversion to non-affective psychosis in
ultra-high risk individuals.
Amminger GP, Leicester S, Yung AR, Phillips LJ, Berger GE, Francey SM, Yuen HP,
OBJECTIVE: We examined if age of onset of psychiatric symptoms and/or sex predict conversion to non-affective or affective psychosis in individuals considered to be at ultra-high risk for schizophrenia.
METHOD: Participants (n=86) were offered treatment and monthly follow-up until transition to psychosis, or for 12months if they did not meet exit criteria for psychotic disorder. Individuals without transition to psychosis at 12-month were reassessed approximately 3years after the end of the treatment phase. Ultra-high risk was defined by the presence of subthreshold and/or self-limiting psychotic symptoms and/or having a family history of psychotic disorder combined with functional decline. Cox regressions after adjustment for treatment interventions were applied to investigate associations between age of onset, sex, and other baseline measures with progression to psychotic outcomes.
RESULTS: Early age of onset of psychiatric symptoms, in particular onset before age 18 was the only tested variable that significantly predicted non-affective psychosis. Independent significant predictors of affective psychosis were poor functioning, female sex and the presence of a combination of intake criteria (family history of psychosis plus drop in functioning, and attenuated and/or brief limited sychotic symptoms) at baseline.
CONCLUSIONS: Age of onset of psychiatric symptoms is the single most important factor associated with conversion to non-affective psychosis in ultra-high risk individuals.
Nervenarzt. 2006 Jan;77(1):23-34.
Schizophr Res 2002 Dec 1;58(2-3):185-8
Caudate volume changes in first episode psychosis parallel the effects of normal aging: a 5-year follow-up study.
Tauscher-Wisniewski S, Tauscher J, Logan J, Christensen BK, Mikulis DJ, Zipursky RB.
We investigated whether the caudate nuclei volume (CNV) of 15 first episode psychosis patients increased after 5 years of treatment with either atypical antipsychotics or low doses of typical antipsychotics. Caudate volumes were measured from magnetic resonance imaging (MRI) scans in 15 patients and 10 healthy controls. Both groups demonstrated a significant 9% decline in caudate volume. We were unable to replicate previous reports of caudate enlargement in patients receiving antipsychotic treatment.
J Clin Psychiatry 2002 Nov;63(11):992-7
Quetiapine: an effective antipsychotic in first-episode schizophrenia despite only transiently high dopamine-2 receptor blockade.
Tauscher-Wisniewski S, Kapur S, Tauscher J, Jones C, Daskalakis ZJ, Papatheodorou G, Epstein I, Christensen BK, Zipursky RB.
BACKGROUND: It has been suggested that transiently high dopamine-2 (D(2)) receptor occupancy by antipsychotic medication may be sufficient for inducing an antipsychotic response. We treated patients experiencing their first episode of schizophrenia with a single daily dose of quetiapine to achieve a transient daily peak of D(2) receptor blockade, to determine if this would lead to an antipsychotic response. METHOD: Fourteen patients with a DSM-IV diagnosis of schizophrenia or schizophreniform or schizoaffective disorder were treated with quetiapine titrated to a single daily dose (mean +/- SD dose at the time of the positron emission tomography [PET] scan = 427 +/- 69 mg) for 12 weeks. Peak D(2) occupancy approximately 2 hours postdose and trough D(2) occupancy approximately 20 hours postdose were determined using PET and [(11)C]raclopride. Clinical symptoms and side effects were measured at baseline and every 2 weeks during the treatment phase. RESULTS: Quetiapine administration led to a mean peak D(2) occupancy of 62% +/- 10% 2 hours postdose, which declined to 14% +/- 8% approximately 20 hours postdose. Ten (71%) of 14 patients responded to treatment with quetiapine, scoring "much improved" or greater on the Clinical Global Impressions-Improvement scale. Plasma drug levels and peak D(2) occupancy were highly correlated (r = 0.84; p =.003), as were prolactin and plasma drug levels when measured 2.5 hours after drug administration (r = 0.60; p <.05). Mean weight gain for the 10 subjects who completed the 12-week study was 4.2 +/- 4.6 kg (9.3 +/- 10.2 lb). No clinically relevant motor side effects occurred during the trial. CONCLUSION: Patients with a first episode of schizophrenia responded to treatment with a single daily dose of quetiapine despite only transiently high D(2) receptor occupancy. Our findings raise the question of whether continuously high D(2) blockade is necessary for obtaining an antipsychotic response. Future studies aimed at evaluating the relative merits of "transiently high" versus "continuously high" D(2) occupancy are warranted.
Br J Psychiatry 2002 Aug;181:164; discussion 165
Estimating cognitive deterioration in schizophrenia.
Amminger GP, Edwards J, McGorry PD.
Psychiatr Prax 2002 May;29(4):214-7
Autocastration of a young schizophrenic man
Gossler R, Vesely C, Friedrich MH.
OBJECTIVE: Self-mutilation of the genitals in man is a rare phenomenon mainly occurring in young males. The importance of conflicts about the male role, difficulties with the male identification in childhood and feeling of guilt for sexual offences are discussed in the literature. The influence of developmental crisis on this symbolic form of automutilation will be discussed in our case report. METHOD: We present a case of a young schizophrenic man whose illness started in adolescence. He committed genital automutilation already in early adolescence, as a young male he autocastrated himself. DISCUSSION: We demonstrate the connection of specific problems of development in adolescence and psychopathology. Autocastration will be discussed as a "psychotic" solution of the adolescent conflict of dependence. CONCLUSIONS: Developmental conflicts may be important pathoplastic factors who may lead to severe psychopathology and misbehavior. Additionally to a psychopharmacological treatment a specific adolescent- and conflictoriented psychotherapy for solving the developmental conflicts in young schizophrenic patients should be established.
Psychol Med 2002 Apr;32(3):563-4
Duration of untreated psychosis (DUP) and outcome in schizophrenia.
Edwards J, Harrigan SM, McGorry PD, Amminger PG.
Schizophr Res 2002 Apr 1;54(3):223-30
Duration of untreated psychosis and cognitive deterioration in first-episode schizophrenia.
Amminger GP, Edwards J, Brewer WJ, Harrigan S, McGorry PD.
Cognitive impairment is an important clinical feature in many individuals with schizophrenia. Factors associated with cognitive deficit are not well established. Duration of untreated psychosis (DUP) has recently gained interest as a prognostic factor in schizophrenia. This study reports on the association between DUP and cognitive function. Subjects comprised 42 individuals (30 males, 12 females) who experienced a first-episode of DSM-III-R schizophrenia or schizophreniform disorder. Cognitive function was determined at clinical stabilization using the WAIS-R. An estimate of cognitive deterioration was based on the WAIS-R subtest profile. Longer DUP, male gender, higher premorbid IQ and younger age at admission independently predicted cognitive deterioration. Poorer performance on Digit Symbol and Comprehension subtests was associated with longer DUP. The findings suggest that untreated psychosis compromises some aspects of cognitive function. Studies investigating the association between DUP and outcome should control for potentially confounding variables. Early treatment of psychosis could help to reduce the prominent cognitive deficit in first-episode schizophrenia.
Psychopharmacology (Berl) 2001 Sep;157(3):236-42
In vivo (123)I IBZM SPECT imaging of striatal dopamine 2 receptor occupancy in schizophrenic patients.
Barnas C, Quiner S, Tauscher J, Hilger E, Willeit M, Kufferle B, Asenbaum S, Brucke T, Rao ML, Kasper S.
RATIONALE: Single photon emission computed tomography (SPECT) using (123)I iodobenzamide (IBZM) as tracer substance has been shown to be a useful tool to visualize dopamine 2 (D2) receptor occupancy. OBJECTIVES: We investigated the striatal D2 receptor occupancy of zotepine which is referred to the class of atypical antipsychotic drugs. METHODS: (123)I IBZM and SPECT were used to visualize striatal dopamine 2 (D2) receptor occupancy in zotepine-treated schizophrenic patients. Two groups of schizophrenic patients receiving either 150 mg/day zotepine (n=6) or 300 mg/day (n=6) underwent examination. For the quantification of striatal D2 receptor occupancy, striatal IBZM binding in patients treated with antipsychotics was compared to untreated healthy controls (n=8) reported earlier. RESULTS: Zotepine led to a mean overall striatal D2 receptor occupancy of 73%. Patients with 150 mg daily showed a significantly lower occupancy (65.8%, SD=6.2) than patients with 300 mg/day (77.8%, SD=10.7; P<0.05). No clinically relevant extrapyramidal side effects occurred during treatment with zotepine. CONCLUSIONS: There was no correlation between the degree of striatal D2 receptor occupancy and clinical improvement.
Am J Psychiatry 2001 Jul;158(7):1161-3 Comment on: Am J Psychiatry. 2000 May;157(5):808-15.
Untreated initial psychosis.
McGorry PD, Harrigan SM, Amminger P, Norman R, Malla A.
Int Clin Psychopharmacol 2001 May;16(3):163-8
Zotepine in the treatment of acute hospitalized schizophrenic episodes.
Kasper S, Quiner S, Barnas C, Fabisch H, Haushofer M, Sackel C, Konig P, Lingg A, Platz T, Rittmannsberger H, Stuppack C, Willeit M, Zapotoczky HG.
The atypical antipsychotic zotepine was studied in an open, multicentre uncontrolled, post-marketing surveillance study in 108 schizophrenic patients hospitalized in 12 trial centres in Austria. Within the dosage range of 50-450 mg (mean at the end of the study, 207 +/- 125 mg/day), a significant reduction of positive as well as negative symptoms was noted. There was no increase in extrapyramidal side-effects during the study and a significant decrease in akathisia scores. The medication was well tolerated during the 42-day observation period. Zotepine improved both positive and negative symptoms and was not accompanied by extrapyramidal side-effects, justifying its classification as an atypical antipsychotic.
Acta Psychiatr Scand 2000 Dec;102(6):414-22
Premorbid performance IQ deficit in schizophrenia.
Amminger GP, Schlogelhofer M, Lehner T, Looser Ott S, Friedrich MH, Aschauer HN.
OBJECTIVE: Performance IQ (PIQ) is often lower than verbal IQ (VIQ) in schizophrenic patients. Whether PIQ < VIQ precedes psychotic symptoms in schizophrenia remains uncertain. METHOD: We investigated premorbid IQ scores in 63 subjects assessed at a child and adolescent psychiatric unit (mean age 13.1 years, SD 3.2), who at follow-up in adulthood (mean age 30.9 years, SD 3.9) received a lifetime RDC diagnosis of schizophrenia-related psychosis, affective disorder, or no psychiatric disorder. RESULTS: Premorbid PIQ < VIQ significantly differentiated the groups with schizophrenia-related psychosis and no psychiatric disorder. Subjects with schizophrenia-related psychosis had a significantly lower mean value for premorbid PIQ, but not VIQ, compared to subjects who developed affective disorder or subjects without psychiatric disorder. CONCLUSION: Our results emphasize premorbid intellectual deficits in schizophrenia. Those deficits might largely be in consequence of an impairment on the PIQ scale.
J Nerv Ment Dis 2000 Nov;188(11):751-6
The New York High-Risk Project: comorbidity for axis I disorders is preceded by childhood behavioral disturbance.
Amminger GP, Pape S, Rock D, Roberts SA, Squires-Wheeler E, Kestenbaum C, Erlenmeyer-Kimling L.
The relationship between childhood behavioral disturbance and comorbidity for adult psychiatric disorders has not been sufficiently investigated. Subjects of this report (N = 185) were offspring of parents with schizophrenia or affective disorder and of normal parents from the New York High-Risk Project. Data on childhood behavior at the mean age of 9.5 years were obtained in a parent interview at initial assessment in 1971-72. Adulthood outcomes were assessed through standardized interviews, and lifetime axis I diagnoses were based on Research Diagnostic Criteria. Subjects with comorbidity for axis I disorders exhibited significantly more behavioral problems as children, compared with those who developed either one or no psychiatric disorder in adulthood. This association was not biased by gender or parental diagnosis of psychiatric disorder. The findings emphasize that psychiatric comorbidity can be traced back to childhood and underline the importance of longitudinal observations in psychiatric research.
Int Clin Psychopharmacol 2000 Jan;15(1):57-60
Remission of severe tardive dyskinesia in a schizophrenic patient treated with the atypical antipsychotic substance quetiapine.
Vesely C, Kufferle B, Brucke T, Kasper S.
In a single inpatient case study, a schizophrenic patient with tardive dyskinesia after prolonged treatment with typical neuroleptics was treated with the new atypical neuroleptic quetiapine, a dibenzothiazepin-derivative. Within 2 weeks of treatment with quetiapine, symptoms of tardive dyskinesia improved; 10 weeks after starting treatment tardive dyskinesia stopped completely. Over the same period, dopamine D2 receptor occupancy decreased substantially, as measured by IBZM-SPECT after 14 and 77 days of treatment.
Am J Psychiatry 1999 Apr;156(4):525-30
Relationship between childhood behavioral disturbance and later schizophrenia in the New York High-Risk Project.
Amminger GP, Pape S, Rock D, Roberts SA, Ott SL, Squires-Wheeler E, Kestenbaum C, Erlenmeyer-Kimling L.
OBJECTIVE: An association between childhood behavioral disturbance and adulthood schizophrenia has been seen previously in retrospective or follow-back studies and in prospective studies. The authors examined the relationship between childhood behavioral problems and adulthood schizophrenia-related psychoses. Because a high rate of childhood behavioral problems is known to be associated with adult substance abuse, these analyses controlled for substance abuse. METHOD: The subjects of this investigation (N = 185) were offspring of parents with schizophrenia or affective disorder and of normal parents from the New York High-Risk Project (sample A). Data on childhood behavioral problems were obtained in a parent interview at initial assessment in 1971-1972. Adulthood outcomes (schizophrenia-related psychoses, affective disorders, anxiety disorders, substance abuse) were based on lifetime axis I diagnoses according to the Research Diagnostic Criteria. RESULTS: Substance abuse had a significant interaction with the clinical outcome groups. In subjects without substance abuse, those with schizophrenia-related psychoses had exhibited significantly more behavioral problems as children than had adult offspring with affective or anxiety disorder or with substance abuse only or no disorder. CONCLUSIONS: These results support the view that schizophrenia-related psychoses can be followed back to early behavioral disturbances. The confounding effects of substance abuse should be statistically controlled in studies of longitudinal associations between childhood behavioral disturbance and axis I outcomes.
Eur Arch Psychiatry Clin Neurosci 1999;249 Suppl 4:83-9
Dopamine- and serotonin-receptors in schizophrenia: results of imaging-studies and implications for pharmacotherapy in schizophrenia.
Kasper S, Tauscher J, Kufferle B, Barnas C, Pezawas L, Quiner S.
Considerable progress has been achieved over the past 15 years in uncovering the biological basis of major psychiatric disorders. Since psychopharmacological treatment is thought to act on the underlying biological basis of the disease, brain imaging techniques enable us to understand the mechanism of action of such compounds. Positron emission tomography (PET) as well as single photon emission computerized tomography (SPECT) are important tools used to determine patterns of brain dysfunction and to uncover the mechanism of action for antipsychotic compounds. These techniques allow us to determine striatal D2 receptor as well as cortical 5-HT2A receptor occupancy rates which are linked, at least partly, to clinical efficacy as well as side effect rates. In general it has been shown that atypical antipsychotics have a lower striatal D2 receptor occupancy rate than typical antipsychotics, parallelling the more favorable extrapyramidal side effects of atypical antipsychotics, and as a group effect they have a high 5-HT2A occupancy compared to low rates for typical agents. However, there is no association between striatal D2 receptor occupancy rates and antipsychotic efficacy but 5-HT2A occupancy rates are associated with favorable treatment for depressive symptoms within schizophrenia and improvement of cognitive function. The availability of ligands for measurement of extrastriatal D2 receptors or different 5-HT receptors (e.g. 5-HT1A) will further shed light on the pathophysiology of schizophrenia as well as possible psychopharmacological treatment perspectives.
Schizophr Res 1998 May 4;31(1):1-11
The New York High-Risk Project: social and general intelligence in children at risk for schizophrenia.
Ott SL, Spinelli S, Rock D, Roberts S, Amminger GP, Erlenmeyer-Kimling L.
Social deficits, as well as low performance on intelligence tests, are known early symptoms of schizophrenia. We studied whether impairment of social intelligence can be detected before the outbreak of the disorder. In the New York High-Risk Project, children at risk for schizophrenia (HRSz) or affective disorder (HRAff) and a normal control group (NC) were studied over the past 26 years. The children are now in mid-adulthood, with known psychiatric outcomes. Developmental and clinical data from childhood can now be related to adulthood diagnoses. We compared mean WISC (or WISC-R) and WAIS (or WAIS-R) scores from childhood and adolescence, and change of IQ, between the risk groups, as well as between the adulthood outcomes. We were specifically interested in the development of social intelligence (the Picture Arrangement and Comprehension subtests). We used logistic regression analyses to generate a model predicting adulthood schizophrenia. Results: IQ at age 9,7 was lower in children with HRSz than with HRAff. Adulthood schizophrenia, compared with major depressive disorder and no psychiatric diagnosis could not be related conclusively to low IQ. This may be a result of the study design, since children with IQ below 70 or behavioral problems were not eligible as study subjects. There was no evidence of lower scores or more decline in social intelligence related to age or group membership (risk or outcome). Subtest-Scatter, a nondirectional measure of the differences between all subtests and Vocabulary, reflecting a lesser difference between crystallized and fluid intelligence, was identified as a significant predictor of adulthood schizophrenia, in the whole group as well as in the HRSz group alone.
Eur Child Adolesc Psychiatry 1997 Dec;6(4):212-8
Premorbid adjustment and remission of positive symptoms in first-episode psychosis.
Amminger GP, Resch F, Mutschlechner R, Friedrich MH, Ernst E.
The impact of premorbid social and intellectual functioning in childhood and early adolescence on the developmental course of schizophrenia is not sufficiently understood. In a retrospective case study (93 consecutive in-patients, 43 males and 50 females) of first-episode psychosis occurring in adolescence, the relationship between premorbid adjustment and short-term therapeutic outcome under treatment conditions was examined. All of the patients had a DSM-III-R diagnosis of schizophrenia (n = 56) or schizo-affective disorder (n = 37). The mean age of the patients at the time of the study was 15.8 (SD = 1.0). Premorbid functioning during childhood and early adolescence was assessed by using the Cannon-Spoor et al. Premorbid Adjustment Scale (PAS) and studied with respect to its prognostic relevance for short-term therapeutic outcome (eight weeks) under neuroleptic treatment (350-700 mg Chlorpromazin dose equivalent). Criteria for clinical outcome were obtained from the study by Pearlson et al. (1989) which defines three grades (complete remission, partial remission and no response), according to the degree of positive symptomatology. Statistical analysis was based on nonparametric variance analysis. Patients with complete remission of positive symptoms after eight weeks of therapy had experienced far better premorbid adjustment in early adolescence and in childhood. Diagnosis and gender did not bias this result. Our data suggest that premorbid social functioning is a crucial variable with regard to therapeutic outcome in first-episode psychosis. Previous studies have reported a relation between poor premorbid functioning and negative symptoms. We found premorbid adjustment related to the course of positive symptoms.
Psychopharmacology (Berl) 1997 Oct;133(4):323-8
IBZM SPECT imaging of striatal dopamine-2 receptors in psychotic patients treated with the novel antipsychotic substance quetiapine in comparison to clozapine and haloperidol.
Kufferle B, Tauscher J, Asenbaum S, Vesely C, Podreka I, Brucke T, Kasper S.
We investigated the striatal dopamine-2 (D2) receptor occupancy caused by different antipsychotic substances in 18 psychotic patients (16 with schizophrenic and two with schizoaffective disorder according to DSM-IV) with single photon emission computed tomography (SPECT) using 123I-iodobenzamide (IBZM) as tracer substance. Four patients were treated with the novel antipsychotic compound quetiapine (300-700 mg/day), six with clozapine (300-600 mg/ day) and eight with haloperidol (10-20 mg/day). They were compared with eight healthy controls. Measurement of S/F ratios and consecutive calculation of D2 receptor occupancy revealed a significantly lower striatal D2 occupancy rate with quetiapine and clozapine in comparison to haloperidol. In correspondence with the low striatal D2 receptor occupancy rates and again in contrast to the haloperidol treatment group, there were no extrapyramidal motor side-effects (EPS) in the quetiapine and clozapine treatment groups. Therefore, the reported data support the position that quetiapine can be considered to be an atypical antipsychotic substance due to its relatively weak striatal D2 receptor blocking property and therefore its low propensity to induce EPS.
Psychiatry Res 1996 Nov 25;68(1):23-30
Striatal dopamine-2 receptor occupancy in psychotic patients treated with risperidone.
Kufferle B, Brucke T, Topitz-Schratzberger A, Tauscher J, Gossler R, Vesely C, Asenbaum S, Podreka I, Kasper S.
Seventeen psychiatric patients (11 with schizophrenia, 5 with other psychotic disorders, and 1 with obsessive-compulsive disorder) were examined by single photon emission computed tomography with 123I-iodobenzamide (IBZM) as tracer. Patients were treated with risperidone in two different dosage groups (3 mg and 8 mg) and haloperidol (10-20 mg) and compared with eight healthy control subjects. There was a statistically significant difference in basal ganglia/frontal cortex ratios of IBZM binding between controls and all treatment groups. A statistically significant difference was also found concerning these ratios and percentage of dopamine D2 receptor occupancy rates between the treatment groups with lowest ratios and highest percentage of D2 receptor occupancy in the group of patients treated with haloperidol, followed by the group treated with 8 mg of risperidone and the group treated with 3 mg of risperidone.
Nervenarzt 1997 May;68(5):438-40 Comment on: Nervenarzt. 1996 Jul;67(7):558-63.
"Primary and secondary negative symptoms: a reliable differentiation?" Comment on the contribution by W. Barnett et al.
Amminger GP, Kirkpatrick B.
Br J Psychiatry 1994 Aug;165(2):273 Comment on: Br J Psychiatry. 1994 Feb;164(2):202-7.
Social competence and adolescent psychosis.
Amminger GP, Mutschlechner R, Resch F.
European-Child-and-Adolescent-Psychiatry. 1993 Jul; Vol 2(3): 155-160
Natural killer cell function in adolescent and adult schizophrenic patients.
Resch,-Franz; Amminger,-G-Paul; Aschauer,-Harald; Mueller,-Christian; et-al
Studied natural immunology in schizophrenic patients to elucidate differential effects of psychopathological status and neuroleptic treatment. Natural killer (NK) cell activity and antibody dependent cellular cytoxicity (ADCC) were tested in 24 adolescent schizophrenic patients (aged 14-18 yrs) and compared with 27 adult schizophrenics (aged 20-56 yrs) and 73 healthy controls. Age of psychopathological status did not have a significant impact on NK activity or ADCC. There were no significant general effects resulting from neuroleptic treatment on NK activity detectable in patients tested before and during treatment. However, there was a significant negative correlation between the differences of NK activity (before and during treatment) and the NK activity before treatment.
Z Kinder Jugendpsychiatr 1992 Mar;20(1):5-11
Side effects of clozapine in therapy of psychotic disorders in adolescents. A retrospective clinical study
Amminger GP, Resch F, Reimitz J, Friedrich MH.
A retrospective study was conducted of 53 consecutive inpatients (through 1990) with psychotic disorders. The patients were between 13 and 18 years of age. In all cases this was the first time they had been treated with clozapine. The adverse effects seen under clozapine are discussed. During the use of clozapine assessments were made of liver enzymes, leukocytes, blood pressure and body temperature. There was an increase in liver enzyme values in 37.7% of the patients, leukopenia under 4000/mm3 in 15.1%, an increase in body temperature in 3.8% and bradycardia together with hypotensive dysregulation in 1.9%.
Z Klin Psychol Psychopathol Psychother 1990;38(1):15-20
Developmental psychological aspects of schizophrenic thinking
Resch F, Strobl R, Schuch B, Oppolzer A.
Based on a phenomenological analysis of psychotic interpretation of the world concretism is supposed to represent an important mechanism of schizophrenic thinking: Schizophrenic concretism is the result of an ontological regression of cognitive functioning onto the archaic level of actional representation. Following Jean Piaget's theories about the children's constructions of reality a hypothesis about the structure of psychotic interpretations of the world is being proposed: In psychotic thinking the knowledge about the world is structured in an adualistic way which is characterized by an alloy of significance and notion, inner and outer world, physis and psyche. The structural similarity of psychotic thinking and thinking in early developmental stages is illustrated concretely on the basis of examples. Fundamental differences between childish and schizophrenic ways of interpreting the world will be presented, showing the specificity of cognitive representation in schizophrenic thinking.
Bibl Psychiatr 1983;(163):1-141
Adoleszentenpsychosen. Adolescent psychoses. Pathoplastic and psychopathologic criteria
Acta Paedopsychiatr 1980 Sep;46(1-2):21-30
Differentialdiagnose der Schizophrenien im Kindes- und Jugendalter
Anhand von 28 jugendlichen psychotischen Patienten wurde nach maximal fuenf Jahren Beobachtungs- und Betreuungsdauer ein Diagnostikvergleich nach den Psychosekriterien von Bleuler, Schneider und Berner durchgefuehrt. In der Kontrolldiagnose nach Bleuler ergab sich aus 22 Schizophrenien und sechs Affektpsychosen ein Wandel in 16 Schizophrenien, acht Affektpsychosen und vier "borderline cases". Nach Berner wurden die 14 endomorph-zyklothymen Patienten gleichdiagnostiziert und die 14 endomorph-schizophrenen Psychosen in 13 weiterhin bestehenden endomorph-schizophrene und eine schizoaffektive abgewandelt. Die nach Schneiders Kriterien diagnostizierten neun Schizophrenien behielten auch nach der Beobachtungsdauer ihre Diagnose bei. Nach einleitender theoretischer Darstellung der Diagnosekriterien wird der Wechsel der Diagnosen im Beobachtungszeitraum dargestellt.