Prodromal Symptoms Of Schizophrenia Research Articles

Prodromal symptoms of schizophrenia: What to look for

Prodromal symptoms of schizophrenia: What to look for

Smaller subcortical volumes and enlarged lateral ventricles are associated with higher global functioning in young adults with 22q11.2 deletion syndrome with prodromal symptoms of schizophrenia

The 22q11.2 deletion syndrome (22q11DS) is a developmental genetic syndrome associated with a 30% risk for developing schizophrenia. Lateral ventricles and subcortical structures are abnormal in this syndrome as well as in schizophrenia. Here, we investigated whether these structures are related in young adults with 22q11DS with and without prodromal symptoms (PS) for schizophrenia and whether abnormalities in volumes are associated with global functioning. MR images were acquired on a 3T scanner from 51 individuals with 22q11DS and 30 healthy controls (mean age: 21±2 years). Correlations were performed to evaluate the relationship between ventricular and subcortical volumes, with Global Assessment of Functioning (GAF) and Premorbid Adjustment Scale (PAS) in each group. Lateral ventricular volumes correlated negatively with subcortical volumes in individuals with 22q11DS. In individuals with 22q11DS with PS only, GAF correlated positively with volumes of the lateral ventricles and negatively with subcortical volumes. PAS correlated negatively with lateral ventricle volumes, and positively with volumes of subcortical structures. The results suggest a common neurodevelopmental mechanism related to the growth of these brain structures. Further, the ratio between the volumes and clinical measures could potentially be used to characterize individuals with 22q11DS and those from the general population for the risk of the development of schizophrenia.

Enlarged Lateral Ventricles and Smaller Subcortical Volumes are Associated With Better Premorbid Adjustment in Young Adults With 22q11.2 Deletion Syndrome With Prodromal Symptoms of Schizophrenia

The sizes of lateral ventricles and subcortical structures are abnormal in schizophrenia, and in 22q11.2 deletion syndrome (22q11DS), a developmental genetic syndrome associated with a 30% risk for developing schizophrenia. Here we investigated whether lateral ventricles and subcortical volumes are related in young adults with 22q11DS with and without prodromal symptoms (PS) of schizophrenia and whether abnormalities in volumes are associated with premorbid adjustment.

Abnormalities in white matter tracts in the fronto-striatal-thalamic circuit are associated with verbal performance in 22q11.2DS

BackgroundAbnormalities in fronto-striatal-thalamic (FST) sub-circuits are present in schizophrenia and are associated with cognitive impairments. However, it remains unknown whether abnormalities in FST sub-circuits are present before psychosis onset. This may be elucidated by investigating 22q11.2 deletion syndrome (22q11DS), a genetic syndrome associated with a 30% risk for developing schizophrenia in adulthood and a decline in Verbal IQ (VIQ) preceding psychosis onset. Here, we examined white matter (WM) tracts in FST sub-circuits, especially those in the dorsolateral (DLPFC) and ventrolateral prefrontal cortex (VLPFC) sub-circuits, and their associations with VIQ in young adults with 22q11DS. MethodsDiffusion MRI scans were acquired from 21 individuals with 22q11DS with prodromal symptoms of schizophrenia, 30 individuals with 22q11DS without prodromal symptoms, and 30 healthy controls (mean age: 21 ± 2 years). WM tracts were reconstructed between striatum and thalamus with rostral middle frontal gyrus (rMFG) and inferior frontal gyrus (IFG), representing DLPFC and VLPFC respectively. Fractional anisotropy (FA) and radial diffusivity (RD) were used for group comparisons. VIQ was assessed and associations with the diffusion measures were evaluated. ResultsFA was significantly increased and RD decreased in most tracts of the DLPFC and VLPFC sub-circuits in 22q11DS. Verbal IQ scores correlated negatively with FA and, at trend level, positively with RD in the right thalamus-IFG tract in 22q11DS with prodromal symptoms. ConclusionsWhile abnormalities in FST sub-circuits are associated with schizophrenia, we observed that these abnormalities are also present in 22q11DS individuals with prodromal symptoms and are associated with verbal performance in the right thalamus-IFG tract.

UNDERSTANDING SCHIZOPHRENIA, UNIFYING THE PHENOMENOLOGICAL AND COGNITIVE SCIENCES APPROACHES

Both philosophy and cognitive science have made valuable contributions towards accounting for the aetiology of Schizophrenia, an illness that possesses a disparate assortment of symptoms. However, there is no firm agreement on what causes such experiences to arise. A theory is proposed which simplifies the signs and symptoms of Schizophrenia and is something which does not appear to exist in the field to date. The model proposed is a hybrid theory, combining the phenomenological approach of Sass and Parnas with elements from Frith and Hemsley’s cognitive science perspective. An argument is that if a hybrid theory was used it would assist in the early intervention of Schizophrenia by providing a focus for treatment during developmental stages. Keywords: psychiatric practice, cognitive science, early intervention in Schizophrenia, prodromal symptoms in Schizophrenia, unification of symptom clusters in Schizophrenia.

Common genetic variants have associations with human cortical brain regions and risk of schizophrenia.

Schizophrenia is a highly heritable mental disorder and is reported to be associated with measurements in cortical regions of the human brain. In this study, we considered genome-wide association studies to uncover genetic effects on cortical regions and prodromal symptoms of schizophrenia. Specifically, area, thickness, and volume of 66 cortical regions derived from magnetic resonance imaging scans of 1,445 children and adolescents from the Philadelphia Neurodevelopmental Cohort were studied. Two common variants were identified as being associated with two prefrontal cortical regions (one significant variant rs11601331 on chromosome 11p11 for right rostral middle frontal gyral area, p = 1.97 × 10 -8 ; one suggestive variant rs2345981 on chromosome 6q11 for left frontal pole gyral volume, p = 2.07 × 10 -7 ), where the significance of rs11601331 was independently replicated on the Pediatric Imaging, Neurocognition, and Genetics study of size 1,239 (p = 9.19 × 10 -3 ). Moreover, genetic effects on schizophrenia were investigated based on a sample of 8,719 subjects. The two identified variants rs11601331 and rs2345981 showed significant association with the longest prodromal symptoms duration (p = 0.048 and p = 0.027, respectively).

Polyunsaturated fatty acid deficiency during neurodevelopment in mice models the prodromal state of schizophrenia through epigenetic changes in nuclear receptor genes

The risk of schizophrenia is increased in offspring whose mothers experience malnutrition during pregnancy. Polyunsaturated fatty acids (PUFAs) are dietary components that are crucial for the structural and functional integrity of neural cells, and PUFA deficiency has been shown to be a risk factor for schizophrenia. Here, we show that gestational and early postnatal dietary deprivation of two PUFAs—arachidonic acid (AA) and docosahexaenoic acid (DHA)—elicited schizophrenia-like phenotypes in mouse offspring at adulthood. In the PUFA-deprived mouse group, we observed lower motivation and higher sensitivity to a hallucinogenic drug resembling the prodromal symptoms in schizophrenia. Furthermore, a working-memory task-evoked hyper-neuronal activity in the medial prefrontal cortex was also observed, along with the downregulation of genes in the prefrontal cortex involved in oligodendrocyte integrity and the gamma-aminobutyric acid (GABA)-ergic system. Regulation of these genes was mediated by the nuclear receptor genes Rxr and Ppar, whose promoters were hyper-methylated by the deprivation of dietary AA and DHA. In addition, the RXR agonist bexarotene upregulated oligodendrocyte- and GABA-related gene expression and suppressed the sensitivity of mice to the hallucinogenic drug. Notably, the expression of these nuclear receptor genes were also downregulated in hair-follicle cells from schizophrenia patients. These results suggest that PUFA deficiency during the early neurodevelopmental period in mice could model the prodromal state of schizophrenia through changes in the epigenetic regulation of nuclear receptor genes.

Blood Test May Predict Patients Likely to Develop Schizophrenia

When combined with the scores from a clinical assessment, the test was able to predict individuals with prodromal symptoms of schizophrenia who later developed the disorder with 90 percent accuracy.

The Second Revision of the Dopamine Theory of Schizophrenia: Implications for Treatment and Drug Development

In this edition of Biological Psychiatry, Egerton et al. (1) from the Institute of Psychiatry at King’s College in London published the results of an imaging study measuring dopamine (DA) synthesis capacity in subjects presenting potentially prodromal symptoms of schizophrenia. Subjects fulfilled clinical criteria associated with a 20% to 40% risk of presenting a psychotic episode within 1 to 3 years (2), a condition labeled as ultra-high risk (UHR). Compared with matched control subjects, striatal DA synthesis capacity (measured with positron emission tomography as the uptake of [F]DOPA) was increased in UHR subjects. Analysis of striatal functional subdivisions showed that the [F] DOPA uptake was increased in the associative striatum (AST) and not in the ventral striatum (VST). This outcome confirms an earlier result from the same group in a smaller cohort (3) and suggests that abnormalities of DA function in the AST precede the emergence of psychotic symptoms in UHR subjects. The authors should be complimented for having submitted their initial findings to the rigor of replication in an independent cohort. As pointed out by the authors, replication of a clinical finding by the same investigators does carry less weight than independent replication. Nonetheless, replication studies are extremely important and might not be given enough attention and credit in the field. Given that the recruitment criteria, clinical evaluation, and imaging technique were maintained between the two studies, the data can be pooled, and this combined analysis will be especially important for the follow-up studies. Based on the UHR criteria, it is anticipated that 20% to 40% of these subjects will present a psychotic episode within 2 years and that this episode might be the first psychotic manifestation of a chronic psychotic disorder such as schizophrenia. In the follow-up of the first cohort, the authors observed that increased [F]DOPA uptake at baseline was associated with higher risk of psychotic transition within 3 years. It will be very important to ascertain if the prognostic value of elevated [F]DOPA uptake in the AST is replicated in this larger cohort. This result provides an important contribution to a large body of imaging work performed over the last decade that generated a remarkably consistent picture of alteration of DA function in schizophrenia [reviewed in (4,5)]. Using either [F]DOPA uptake or competition studies between endogenous DA and DA D2 receptor ligands, several groups have documented that schizophrenia is associated with increases in striatal presynaptic DA function, at least during the period of psychotic exacerbation, and that this increase is associated with the severity and acuity of psychotic symptoms. This DA dysregulation does not appear to be a

2362 – Is it a prodrome of psychosis? Or is it naanxious disorder? A case report

The concept of prodromal symptoms in schizophrenia is an old matter of debate. There have been reported several signs and symptoms that are considered to have a predictive value in a first psychotic episode, namely in the mood or anxious spectrums. However, these symptoms are not specific and can overlap with other disorders that have to be considered in the differential diagnosis. To present a young adult with marked anxious symptoms, namely in obsessive-compulsive spectrum, and psychotic (subclinical) symptoms, questioning the extension of the comorbidity between anxious disorders and schizophrenia. A case report is presented and a literature review of the theme is shortly surveyed. The case report is about a 20 years old man, who have been developing for about two years obsessive thoughts of doubt concerning his sexuality, death and his mental health. Additionally, he described sensations of depersonalization, derealization and an intense distress that have been interfering with his function and daily activity. Several studies report substantial presence of anxious symptoms (including OCD symptoms) in schizophrenia, suggesting its early appearance in the development of the disease. Moreover, they can act as predictor of poorer outcome and may promote transition from psychotic symptoms to schizophrenia. In schizophrenia prodromal stages, anxious symptoms may increase the risk and predict the development of psychosis disorder. On the other hand, the existence of mild psychotic symptoms can be present in neurotic disorders, witch compels clinicians to be cautious in the differential diagnosis that enclose these symptoms.

Schizophrenia knowledge and attitudes toward help-seeking among Japanese fathers and mothers of high school students

The prodromal symptoms of schizophrenia are nonspecific and include social withdrawal, sleeplessness, decreased desire, and loss of concentration. Schizophrenia outcomes might be improved if greater therapeutic effort was focused on people with prodromal symptoms. To hasten help-seeking for schizophrenia, we developed a schizophrenia education program for families of patients. Help-seeking and schizophrenia attitudes and knowledge were analyzed among Japanese parents (666 fathers and 613 mothers) of high school students by using the Social Distance Scale-Japanese version, the Link Devaluation-Discrimination Measure and our own questions on help-seeking and schizophrenia knowledge. Statistical analysis included cross-tabulation, the χ2 test, and multiple regression analysis. Most (97.5%) fathers were aged 40 - 59 years; most (78.3%) mothers were aged 40 - 49 years. There was a significant difference between fathers and mothers in basic knowledge of schizophrenia (P 0.05). When asked what treatment they would seek for a child with sleeplessness or social withdrawal, fathers and mothers significantly differed in seeking help medical care at a department of psychosomatic medicine (P differed between fathers and mothers (P = 0.001). In an analysis of parental response to a child with sleepiness and social withdrawal, multiple regression analysis revealed that fathers and mothers significantly differed in the likelihood of seeking help at a department of psychosomatic medicine and from a school nurse and in the likelihood of not seeking help (P

Higher Levels of Glutamate in the Associative-Striatum of Subjects with Prodromal Symptoms of Schizophrenia and Patients with First-Episode Psychosis

The glutamatergic and dopaminergic systems are thought to be involved in the pathophysiology of schizophrenia. Their interaction has been widely documented and may have a role in the neurobiological basis of the disease. The aim of this study was to compare, using proton magnetic resonance spectroscopy ((1)H-MRS), glutamate levels in the precommissural dorsal-caudate (a dopamine-rich region) and the cerebellar cortex (negligible for dopamine) in the following: (1) 18 antipsychotic-naïve subjects with prodromal symptoms and considered to be at ultra high-risk for schizophrenia (UHR), (2) 18 antipsychotic-naïve first- episode psychosis patients (FEP), and (3) 40 age- and sex- matched healthy controls. All subjects underwent a (1)H-MRS study using a 3Tesla scanner. Glutamate levels were quantified and corrected for the proportion of cerebrospinal fluid and percentage of gray matter in the voxel. The UHR and FEP groups showed higher levels of glutamate than controls, without differences between UHR and FEP. In the cerebellum, no differences were seen between the three groups. The higher glutamate level in the precommissural dorsal-caudate and not in the cerebellum of UHR and FEP suggests that a high glutamate level (a) precedes the onset of schizophrenia, and (b) is present in a dopamine-rich region previously implicated in the pathophysiology of schizophrenia.

Differential propensity in recognition of prepsychotic phenomena among psychiatrists, clinical psychologists and school counsellors

The prodromal symptoms of schizophrenia are difficult to differentiate from other common psychiatric illnesses or stress reactions. Despite the development of new diagnostic instruments, non-specificity and poor awareness of this clinical entity are still major barriers to early identification of individuals at risk for schizophrenia. This study was conducted to assess differences among three types of mental health professionals in the recognition of prepsychotic phenomena. A questionnaire was developed that presented 11 case vignettes. The vignettes represented a hypothetical gradient of clinical severity, including stress reactions; very early stage, intermediate-risk stage and very high-risk stage of the schizophrenia prodrome; and full-blown psychosis. The questionnaire was completed by 57 psychiatrists, 44 clinical psychologists and 50 school counsellors. For each vignette, respondents indicated their top three choices among nine different diagnostic considerations. As a group, psychiatrists were most likely to consider schizophrenia for all stages of clinical severity, whereas school counsellors were least likely to. Still, only about half of psychiatrists selected schizophrenia as their first choice for very high-risk cases, and even fewer psychologists and counsellors did so. A proportion of school counsellors failed to recognize full-blown psychosis. Despite the differential propensity in recognition of prepsychotic phenomena, a gradient in considering schizophrenia as a possible diagnosis across the stages of clinical severity was obvious. Psychiatrists, clinical psychologists and school counsellors all need further education, targeting their group-specific proclivities, to improve their sensitivity and specificity in early identification of individuals at risk for schizophrenia.

Thalamic neurochemical abnormalities in individuals with prodromal symptoms of schizophrenia — Relationship to auditory event-related potentials

Thalamic neurochemical abnormalities may underlie psychotic symptoms and auditory event-related potential (ERP) abnormalities in schizophrenia. We investigated this hypothesis in subjects at risk of psychosis using magnetic resonance spectroscopy and electroencephalography (EEG). Reduced thalamic glutamate plus glutamine and N-acetyl aspartate levels were associated with abnormal frontal ERPs, supporting a thalamic basis for filtering impairments.

P03-352 Aripiprazole in prodromal syndrome of schizophrenia at the male patients with obstetrical traumas in personal medical history

ObjectivesThe prodromal syndrome in schizophrenia can be correlated with a series of neurobiological risk factors, the obstetrical traumas having an important role. The antipsychotic therapy at the male patients with obstetrical traumas in personal medical history can amplify the risk of cerebral structural changes.MethodWe have studied 12 male patients (age 18-20 years), with prodromal schizophrenia syndrome or ARMS, negative symptoms, cognitive disabilities and poor social cognition. All the studied patients present obstetrical traumas in medical personal history, soft extrapyramidal symptoms, facial immobility and facial incapacity to express emotions (behavioral marker for poor social cognition and frontal-amygdala disconectivity). We administered aripiprazole (5mg/day) for 12 months associated with psychokinetotherapy technics, a series of facial mobility standard exercises.ResultsThese patients were evaluated at 6 and 12 months with PANSS, GAF, BARNES scales. The final results are: on the PANSS scale the evolution of negative and cognitive symptoms was ameliorated. The facial mobility and the capacity of emotional expression are also significantly ameliorated. The cognitive abilities and the level of social cognition are evaluated as very good. The extrapyramidal symptoms evaluated on the BARNES scale are not amplifying during the treatment.ConclusionThe facial imobility and the facial incapacity to expressed emotions may be a clinical marker for neurodevelopmental abnormalities in the schizophrenia prodrome. Aripiprazole associated with the psychokinetotherapy technics improve in a significantly way the prodromal symptoms of schizophrenia at the male with obstetrical traumas in medical personal history.

Elevated Striatal Dopamine Function Linked to Prodromal Signs of Schizophrenia

A major limitation on the development of biomarkers and novel interventions for schizophrenia is that its pathogenesis is unknown. Although elevated striatal dopamine activity is thought to be fundamental to schizophrenia, it is unclear when this neurochemical abnormality develops in relation to the onset of illness and how this relates to the symptoms and neurocognitive impairment seen in individuals with prodromal symptoms of schizophrenia. To determine whether striatal dopamine function is elevated in individuals with prodromal symptoms of schizophrenia before the onset of psychosis and to assess how this relates to the symptoms and neurocognitive impairment. Case-control study of in vivo striatal dopaminergic function. Academic research. Patients Patients were recruited from a community mental health service. Twenty-four patients having prodromal symptoms of schizophrenia were compared with 7 patients having schizophrenia and with 12 matched healthy control subjects from the same community. Main Outcome Measure Striatal 6-fluoro-l-dopa F 18-dopa uptake measured using positron emission tomographic (18)F-dopa imaging. Striatal (18)F-dopa uptake was elevated in patients with prodromal symptoms of schizophrenia (effect size, 0.75) to an intermediate degree compared with that in patients with schizophrenia (effect size, 1.25). The elevation was localized in the associative striatum in both groups. Moreover, striatal (18)F-dopa uptake in patients with prodromal symptoms of schizophrenia was correlated with the severity of prodromal psychopathologic and neuropsychological impairment but not with the severity of anxiety or depressive symptoms. These findings indicate that dopamine overactivity predates the onset of schizophrenia in individuals with prodromal psychotic symptoms, is predominantly localized in the associative striatum, and is correlated with the severity of symptoms and neurocognitive dysfunction.

Impaired Sensorimotor Gating of the Acoustic Startle Response in the Prodrome of Schizophrenia

Schizophrenia patients exhibit impairment in prepulse inhibition (PPI) of the acoustic startle response (ASR), which is commonly interpreted as a sensorimotor gating deficit. To date, it is unclear when these gating deficits arise. Results of animal studies and some human data suggest that PPI deficits are in part genetically determined, such that gating deficits could be present before the onset of a full-blown psychosis. To test this assumption, we investigated PPI of ASR in individuals with prodromal symptoms of schizophrenia and patients with first-episode schizophrenia. Startle reactivity, habituation, and PPI of ASR, as well as a neuropsychological test battery, were assessed in 54 subjects with prodromal symptoms of schizophrenia (35 early and 19 late prodromal subjects), 31 first-episode schizophrenia patients (14 unmedicated, 17 medicated), and 28 healthy control subjects. Patients were also examined with the Positive and Negative Syndrome Scale and the Global Assessment of Functioning Scale. Prodromal subjects and unmedicated patients with first-episode schizophrenia showed significant PPI deficits, whereas schizophrenia patients treated with risperidone had almost normal PPI. Startle reactivity decreased with greater severity of symptoms (control subjects, early prodromal group > late prodromal group > unmedicated first-episode patients) but was almost normal in the medicated patients. With respect to habituation, prodromal subjects and schizophrenia patients did not differ from healthy control subjects. PPI disruption is already present in a prodromal state of schizophrenia, but startle reactivity deficits seem to emerge with the onset of acute psychosis.

Impaired sensorimotor gating of the acoustic startle response in the prodrome of schizophrenia

Background Schizophrenia patients exhibit impairment in prepulse inhibition (PPI) of the acoustic startle response (ASR), which is commonly interpreted as a sensorimotor gating deficit. To date, it is unclear when these gating deficits arise. Results of animal studies and some human data suggest that PPI deficits are in part genetically determined, such that gating deficits could be present before the onset of a full-blown psychosis. To test this assumption, we investigated PPI of ASR in individuals with prodromal symptoms of schizophrenia and patients with first-episode schizophrenia. Methods Startle reactivity, habituation, and PPI of ASR, as well as a neuropsychological test battery, were assessed in 54 subjects with prodromal symptoms of schizophrenia (35 early and 19 late prodromal subjects), 31 first-episode schizophrenia patients (14 unmedicated, 17 medicated), and 28 healthy control subjects. Patients were also examined with the Positive and Negative Syndrome Scale and the Global Assessment of Functioning Scale. Results Prodromal subjects and unmedicated patients with first-episode schizophrenia showed significant PPI deficits, whereas schizophrenia patients treated with risperidone had almost normal PPI. Startle reactivity decreased with greater severity of symptoms (control subjects, early prodromal group > late prodromal group > unmedicated first-episode patients) but was almost normal in the medicated patients. With respect to habituation, prodromal subjects and schizophrenia patients did not differ from healthy control subjects. Conclusions PPI disruption is already present in a prodromal state of schizophrenia, but startle reactivity deficits seem to emerge with the onset of acute psychosis.

Randomized, Double-Blind Trial of Olanzapine Versus Placebo in Patients Prodromally Symptomatic for Psychosis

Objective: This study assessed the efficacy of olanzapine in delaying or preventing conversion to psychosis and reducing symptoms in people with prodromal symptoms of schizophrenia. Method: This randomized trial occurred at four North American clinics in the Prevention Through Risk Identification, Management, and Education project. Outpatients received olanzapine (5–15 mg/day, N=31) or placebo (N=29) during a 1-year double-blind treatment period and no treatment during a 1-year follow-up period. Efficacy measures included the conversion-to-psychosis rate and Scale of Prodromal Symptoms scores. Results: During the treatment year, 16.1% of olanzapine patients and 37.9% of placebo patients experienced a conversion to psychosis, a nearly significant difference. The hazard of conversion among placebo patients was about 2.5 times that among olanzapine-treated patients, which also approached significance. In the follow-up year, the conversion rate did not differ significantly between groups. During treatment, the mean score for prodromal positive symptoms improved more in the olanzapine group than in the placebo group, and the mixed-model repeated-measures least-squares mean score showed significantly greater improvement between weeks 8 and 28 with olanzapine. The olanzapine patients gained significantly more weight (mean=8.79 kg, SD=9.05, versus mean=0.30 kg, SD=4.24). Conclusions: A significant treatment difference in the conversion-to-psychosis rate was not demonstrated. However, these results may be influenced by low power. The nearly significant differences suggest that olanzapine might reduce the conversion rate and delay onset of psychosis. Olanzapine was efficacious for positive prodromal symptoms but induced weight gain. Further treatment research in this phase of illness is warranted.

Randomized, Double-Blind Trial of Olanzapine Versus Placebo in Patients Prodromally Symptomatic for Psychosis

This study assessed the efficacy of olanzapine in delaying or preventing conversion to psychosis and reducing symptoms in people with prodromal symptoms of schizophrenia. This randomized trial occurred at four North American clinics in the Prevention Through Risk Identification, Management, and Education project. Outpatients received olanzapine (5-15 mg/day, N=31) or placebo (N=29) during a 1-year double-blind treatment period and no treatment during a 1-year follow-up period. Efficacy measures included the conversion-to-psychosis rate and Scale of Prodromal Symptoms scores. During the treatment year, 16.1% of olanzapine patients and 37.9% of placebo patients experienced a conversion to psychosis, a nearly significant difference. The hazard of conversion among placebo patients was about 2.5 times that among olanzapine-treated patients, which also approached significance. In the follow-up year, the conversion rate did not differ significantly between groups. During treatment, the mean score for prodromal positive symptoms improved more in the olanzapine group than in the placebo group, and the mixed-model repeated-measures least-squares mean score showed significantly greater improvement between weeks 8 and 28 with olanzapine. The olanzapine patients gained significantly more weight (mean=8.79 kg, SD=9.05, versus mean=0.30 kg, SD=4.24). A significant treatment difference in the conversion-to-psychosis rate was not demonstrated. However, these results may be influenced by low power. The nearly significant differences suggest that olanzapine might reduce the conversion rate and delay onset of psychosis. Olanzapine was efficacious for positive prodromal symptoms but induced weight gain. Further treatment research in this phase of illness is warranted.