Biomedical subjects

William G Honer

Publications and source records attributed to William G Honer.

At least 19 recordsLinked to original sources

PubMed2006

The genomic era and perceptions of psychotic disorders: genetic risk estimation, associations with reproductive decisions and views about predictive testing.

As a result of publicity surrounding genetic advances, increasing public awareness of a genetic role in major mental illness may be contributing to a "geneticization" of these illnesses. Geneticization could lead to oversimplified ideas about genetic risk, producing significant social consequences. We sought to investigate perceptions of genetic risk, associated effects on reproductive decisions and attitudes towards genetic testing amongst unaffected relatives of individuals with psychosis. A web-based survey design was used, which all visitors to a psychosis support/information website had the option to complete. Responders were representative of website visitors, and the study design facilitated collection of a large dataset, although the response rate was low. Over-estimating risk was associated with reproductive decisions favoring fewer children, and more positive attitudes towards genetic testing. Facilitating accurate risk perception through genetic counseling could significantly impact reproductive decisions, and the appropriate use of genetic tests in the future.

Adult↗

PubMed2006

Disturbed frontal gyrification within families affected with schizophrenia.

OBJECTIVE: Recently, in a post-mortem and a subsequent structural MR study, a significantly increased gyrification index (GI) was demonstrated in the frontal lobe in individuals with schizophrenia. To examine whether frontal lobe hypergyria is region-specific and whether this might be a suitable endophenotype in the search for the genetic basis of schizophrenia, the frontal as well as parieto-occipital GI were determined in MRI scans of families affected with schizophrenia. METHOD: In the MRI scans of 48 subjects suffering from schizophrenia, in 82 of their first-degree relatives and in 41 control subjects, the GI was determined in three sections anterior to the genu of the corpus callosum and three sections posterior to the splenium, thus allowing for a selective determination of this measure in the frontal as well as the parietal lobe. Outer and inner contours constituting the GI was determined in each section by manual tracing. Statistical analysis was performed using MANOVA with factors diagnostic group and intervening factors from preliminary analyses. RESULTS: The frontal, but not parieto-occipital GI was significantly higher in schizophrenic patients as well as unaffected relatives compared with control subjects (right: 7%, F=13.24, df=3, 155, p<0.0005, left: 6%, F=8.92, df=3, 155, p<0.0005). There was no overall difference between affected and unaffected family members. On the left side however, there was a significant interaction between diagnostic group and genetic loading (F=4.68, df=2, 101, p=0.01): significantly higher GI was found in affected compared with unaffected family members only in uniaffected and not multiaffected families. CONCLUSIONS: These results support our primary finding of hypergyria in the frontal lobe in schizophrenic patients. Compared to the parietal lobe, hypergyria seems to affect the frontal lobe selectively and serves as a suitable neurodevelopmental, possibly even an endophenotypic marker.

Adult↗

PubMed2006

Clozapine alone versus clozapine and risperidone with refractory schizophrenia.

BACKGROUND: The treatment of schizophrenia with multiple antipsychotic drugs is common, but the benefits and risks are not known. METHODS: In a randomized, double-blind study, we evaluated patients with schizophrenia and a poor response to treatment with clozapine. The patients continued to take clozapine and were randomly assigned to receive eight weeks of daily augmentation with 3 mg of risperidone or with placebo. This course of treatment was followed by an optional 18 weeks of augmentation with risperidone. The primary outcome was reduction in the total score for severity of symptoms on the Positive and Negative Syndrome Scale (PANSS). The secondary outcomes included cognitive functioning. RESULTS: A total of 68 patients were randomly assigned to treatment. In the double-blind phase, the mean total score for the severity of symptoms decreased from baseline to eight weeks in both the risperidone and the placebo groups. There was no statistically significant difference in symptomatic benefit between augmentation with risperidone and placebo: 9 of 34 patients receiving placebo and 6 of 34 receiving risperidone responded to treatment (P=0.38). The mean difference in the change in PANSS scores from baseline to eight weeks between those receiving risperidone and those receiving placebo was 0.1 (95 percent confidence interval, -7.3 to 7.0). The verbal working-memory index showed a small decline in the risperidone group and a small improvement in the placebo group (P=0.02 for the comparison between the two groups in the change from baseline). The increase in fasting blood glucose levels was mildly greater in the risperidone group than in the placebo group (16.2 vs. 1.8 mg per deciliter [0.90 vs. 0.10 mmol per liter], P=0.04). The incidence and severity of other side effects did not differ between the two groups. CONCLUSIONS: In this short-term study, the addition of risperidone to clozapine did not improve symptoms in patients with severe schizophrenia. (ClinicalTrials.gov number, NCT00272584).

Adult↗

PubMed2006

DNA copy-number analysis in bipolar disorder and schizophrenia reveals aberrations in genes involved in glutamate signaling.

Using bacterial artificial chromosome (BAC) array comparative genome hybridization (aCGH) at approximately 1.4 Mbp resolution, we screened post-mortem brain DNA from bipolar disorder cases, schizophrenia cases and control individuals (n=35 each) for DNA copy-number aberrations. DNA copy number is a largely unexplored source of human genetic variation that may contribute risk for complex disease. We report aberrations at four loci which were seen in affected but not control individuals, and which were verified by quantitative real-time PCR. These aberrant loci contained the genes encoding EFNA5, GLUR7, CACNG2 and AKAP5; all brain-expressed proteins with known or postulated roles in neuronal function, and three of which (GLUR7, CACNG2 and AKAP5) are involved in glutamate signaling. A second cohort of psychiatric samples was also tested by quantitative PCR using the primer/probe sets for EFNA5, GLUR7, CACNG2 and AKAP5, and samples with aberrant copy number were found at three of the four loci (GLUR7, CACNG2 and AKAP5). Further scrutiny of these regions may reveal insights into the etiology and genetic risk factors for these complex psychiatric disorders.

A Kinase Anchor Proteins↗

PubMed2006

Reduced thalamic volume in patients with chronic schizophrenia after switching from typical antipsychotic medications to olanzapine.

OBJECTIVE: The authors performed a longitudinal study of the effects on thalamic volume of switching from typical to atypical antipsychotic medications. METHOD: Magnetic resonance imaging scans were acquired from 10 subjects with chronic schizophrenia taking typical antipsychotics and 20 healthy volunteers. Subjects with schizophrenia were switched to olanzapine; both groups were rescanned. RESULTS: At baseline, thalamic volumes in subjects with chronic schizophrenia were 5.8% greater than those of healthy volunteers. At follow-up, there was no significant difference between groups. Additional analysis revealed a significant positive correlation between baseline thalamic volume and dosage of typical antipsychotic medication. Higher dosages at baseline were correlated with larger reductions in volume after the switch to olanzapine. CONCLUSIONS: Antipsychotic medication effects may be a factor in the wide range of thalamic volume differences reported between subjects with schizophrenia and healthy volunteers.

Adult↗

PubMed2006

The need for speed: an update on methamphetamine addiction.

The psychostimulant methamphetamine (MA) is a highly addictive drug that has surged in popularity over the last decade in North America. A burgeoning number of clandestine drug laboratories has led to dramatic increases in MA production, which have resulted in significant public health, legal and environmental problems. Current evidence indicates that exposure to MA is neurotoxic, and neuroimaging studies confirm that long-term use in humans may lead to extensive neural damage. These physiological changes are commonly associated with persistent forms of cognitive impairment, including deficits in attention, memory and executive function. In the present review, we provide a comprehensive description of the factors relating to MA use and the major health-related consequences, with an emphasis on MA-induced psychosis. It is hoped that increased knowledge of MA abuse will provide the basis for future treatment strategies.

Amphetamine-Related Disorders↗

PubMed2005

Treatment of a first episode of psychotic illness with quetiapine: an analysis of 2 year outcomes.

BACKGROUND: The first episode of a psychotic disorder provides a unique opportunity to initiate optimal treatment but when a new medication becomes available, little data exist to guide the appropriate use in this population. OBJECTIVES: The objectives were to determine the optimal doses and titration of quetiapine for this group and to measure outcomes (including symptom response, social functioning, mood alterations, motor symptoms, metabolic parameters and cognitive functioning) over 2 years of treatment with quetiapine. DESIGN: Thirty nine subjects with a first episode of psychosis referred to the Nova Scotia Early Psychosis Program in Halifax, Canada, were invited to participate in this study. Standardized clinical, laboratory, and neuropsychological assessments were performed at baseline and following treatment with quetiapine at intervals out to 2 years. RESULTS: Quetiapine was effective in treating the psychotic and mood symptoms while not causing extra-pyramidal signs or symptoms (EPSS). Pre-existing motor dysfunction improved. No anticholinergic medications were required. Several domains of cognitive function also improved (sustained attention, the number of perseverative errors, visuomotor speed and sequencing, verbal fluency and verbal memory). Weight gain was observed along with increases in cholesterol levels but there was no glucose dysregulation. CONCLUSIONS: The results of this two year, naturalistic study of people with a first episode of psychosis indicated that quetiapine was well tolerated and effective for this population. Significant improvements in cognitive functioning also provided evidence for potential longer-term benefits of early and optimal treatment with this agent. However, monitoring metabolic parameters, as recommended for other atypicals, is likely prudent.

Adolescent↗

PubMed2005

A meta-analysis of profile and time-course of symptom change in acute schizophrenia treated with atypical antipsychotics.

The profile and time-course of symptom response in acute schizophrenia is unclear. For the present study, we hypothesized that the time-course would be nonlinear. A meta-analysis was performed using randomized, controlled clinical trials of five atypical antipsychotics reported in nine electronic databases. Studies were of subjects experiencing an acute exacerbation of illness, with multiple BPRS or PANSS data-points as outcome measures. A mixed factorial repeated-measures ANOVA was used. Twenty-one published clinical trials were identified. Reduction in total symptoms from baseline to 4 wk was associated with a linear decline in symptomatology (F=23.4, d.f.=1, 7, p=0.002) without attenuation of effect. In contrast, from baseline to 6 wk the linear symptom reduction (F=76.5, d.f.=1, 12, p<0.001) eventually flattened at the end of the trial (F=87.2, d.f.=1, 12, p<0.001). Secondary analyses showed a similar pattern for typical antipsychotics, and the same profile for risperidone and olanzapine as for atypical agents as a whole. Inclusion of LOCF data altered the results at 4 wk, but not 6 wk; completion rates had no effect on results. In conclusion, this meta-analysis confirms our hypothesis for 6-wk data. The profile of symptom change is one of linear symptom reduction until 4 wk, with a flattening of treatment effects by 6 wk. A curvilinear profile of schizophrenia symptom reduction has possible implications with respect to trial design and clinical decision-making.

Acute Disease↗

PubMed2005

Selective effects of typical antipsychotic drugs on SNAP-25 and synaptophysin in the hippocampal trisynaptic pathway.

Recent studies indicate that levels of presynaptic proteins are altered in the post-mortem brain in schizophrenia. In particular, the hippocampus exhibits reduced levels of synaptophysin and the SNARE protein SNAP-25. The effects of treatment with antipsychotic drugs on levels of SNAP-25 in the hippocampus remains unknown. To determine the effects of typical antipsychotic drugs on levels of synaptophysin and SNAP-25 in the hippocampus, rats were treated with chlorpromazine, haloperidol or trifluoperazine for 21 d. Quantitative immunohistochemistry was used to measure immunoreactivity within the trisynaptic circuit of the hippocampus. Trifluoperazine decreased synaptophysin within the Schaffer collateral region of the radiatum lacunosum in CA1, while haloperidol and chlorpromazine increased SNAP-25 throughout the trisynaptic pathway of the hippocampus, with strongest effects in the mossy fibre region of CA3. These results indicate that presynaptic proteins represent a potential molecular substrate for the effects of antipsychotic drugs on hippocampal synaptic connectivity.

Animals↗

PubMed2005

Ethyl-EPA treatment improves motor dysfunction, but not neurodegeneration in the YAC128 mouse model of Huntington disease.

Huntington disease (HD) is an adult-onset neurodegenerative disorder that is characterized by selective degeneration in the striatum. There are currently no treatments that can prevent the progressive decline of motor and cognitive function in HD. In parallel with a human clinical trial, we examined the efficacy of ethyl-EPA treatment in the YAC128 mouse model of HD. Oral delivery of ethyl-EPA to symptomatic YAC128 mice beginning at 7 months of age increased membrane EPA levels 3-fold (P < 0.001) and resulted in a modest but significant improvement in motor dysfunction by 12 months of age as measured by open-field activity (P = 0.01) and performance on the rotarod (P = 0.05). At this age, ethyl-EPA-treated YAC128 mice showed no improvement in striatal volume, striatal neuron counts, striatal neuronal cross-sectional area, or striatal DARPP-32 expression compared to untreated YAC128 mice, thereby indicating no reduction of striatal neuropathology. This result is congruent with modest motor benefits observed in HD patients treated with ethyl-EPA. Overall, this work demonstrates the feasibility of experimental therapeutics in the YAC128 mouse model and suggests that experiments in these mice may be predictive for future human clinical trials.

Animals↗

PubMed2005

Relation between cerebrospinal fluid, gray matter and white matter changes in families with schizophrenia.

BACKGROUND: Gray matter reduction and ventricular enlargement belong to the best replicated findings in schizophrenia. Brain morphologic changes were also found in non-schizophrenic family members (FM). The intention of this study was to examine whether non-psychotic first-degree relatives reveal similar morphologic changes as schizophrenic patients and how state of genetic loading contribute to these abnormalities. METHODS: Forty-nine schizophrenic patients, 71 non-schizophrenic FM and 48 control subjects took part in this volumetric MRI study. All subjects were between 18 and 59 years old. Dependent variables were gray matter, white matter and total cerebrospinal fluid (CSF) volume, determined by SPM99 segmentation algorithm. As an important part of CSF lateral ventricle volume was determined manually by removing surrounding CSF areas. RESULTS: In schizophrenic patients compared to controls and non-schizophrenic FM total CSF volumes and lateral ventricles were increased. Gray and, to a lesser degree, white matter volumes were decreased as well. For CSF, gray and white matter there was no significant difference between uni- and multiple affected families. CSF correlated significantly negative with gray matter (r=-0.78) and, less intensive, with white matter (r=-0.40). There were negative correlations between gray and white matter volume as well (r=-0.26). These correlations were not significantly different between the diagnostic groups. CONCLUSION: CSF enlargement and gray matter reductions in schizophrenic patients compared to controls and non-affected FM seem to be interdependent findings. However, this correlation is independent of the factor diagnosis and is therefore not specific for schizophrenia.

Adult↗

PubMed2005

Smaller corpus callosum subregions containing motor fibers in schizophrenia.

Neuropsychological and neurophysiological studies provide evidence for abnormal interhemispheric communication in schizophrenia. These abnormalities may have a substrate in structural irregularities of the corpus callosum. This study investigated schizophrenia patients (n=27) and healthy comparison subjects (n=31). Global and regional measurements of the corpus callosum were acquired from one midsagittal SPGR slice. Eight subregions were approximately matched to fiber pathways from cortical regions. Overall effects of diagnosis [Wilks' Lambda F(8,46)=2.45, p=0.03] and diagnosis by age interaction [Wilks' Lambda F(8,46)=2.58, p=0.02] were found in a MANCOVA of the eight functionally specific subregions. Specifically, chronic schizophrenia was associated with a smaller rostral body [lower by 6.9%, F(1,53)=9.70, p=0.003] and anterior midbody [lower by 9.7%, F(1,53)=4.89, p=0.03] subregions. The rostral body and anterior midbody subregions of the corpus callosum primarily have premotor, supplementary motor, and motor cortical fibers transversing through them. Functional abnormalities of the associated cortical regions are reported in schizophrenia. These novel findings suggest that structural abnormalities of the corpus callosum exist in schizophrenia, with perhaps the motor-specific subregions affected more than others. Structural differences in the corpus callosum may be a substrate for interhemispheric functional dysconnectivity in schizophrenia.

Adult↗

PubMed2005

The SNAP-25 gene may be associated with clinical response and weight gain in antipsychotic treatment of schizophrenia.

The synaptosomal-associated protein of 25 kDa (SNAP-25) is an essential component of the core complex that mediates presynaptic vesicle trafficking. Thus, SNAP-25 is directly involved in the release of neurotransmitters. Quantitative alterations of SNAP-25 expression have been reported in brain regions and cerebrospinal fluid (CSF) of schizophrenics and in haloperidol treated rats. This observed altered expression may be influenced by genetic variants of SNAP-25. We hypothesized that polymorphisms of the SNAP-25 gene (sites DdeI, MnlI and TaiI in the 3'UTR) are associated with antipsychotic drug response and induced weight gain. A sample of 59 patients with prior suboptimal response to antipsychotic treatment and diagnosed with DSM-IV schizophrenia or schizoaffective disorder was examined. Patients were administered clozapine, haloperidol, olanzapine or risperidone for up to 14 weeks. Clinical response was defined as the difference between the baseline and the endpoint total scores on the Positive and Negative Syndrome Scale (PANSS). Weight was assessed at baseline and at study endpoint. ANOVA revealed that the MnlI and TaiI polymorphisms were associated with response (F[2,53] = 4.57, p = 0.01 and F[2,52] = 3.53, p = 0.03) and with weight gain (F[2,52] = 4.28, p = 0.01 and F[2,51] = 3.38, p = 0.04). When covariates were included, the MnlI polymorphism remained significantly associated with changes of PANSS scores, but not with weight gain. The DdeI polymorphism was not associated with response or weight gain. These findings suggest that SNAP-25 gene variants affect clinical response in patients with prior poor response to antipsychotics. Weight changes do not seem to be associated with polymorphism of the SNAP-25 gene, however, replication in independent samples is warranted.

Adult↗

PubMed2005

Hippocampal complexin proteins and cognitive dysfunction in schizophrenia.

BACKGROUND: Converging neuroimaging and postmortem evidence indicates synaptic terminals are abnormal in schizophrenia. A putative molecular mechanism implicates abnormalities of proteins involved in the presynaptic secretory machinery, including the modulator proteins complexin I and complexin II. OBJECTIVES: To determine the amount and distribution of complexin proteins in the hippocampus of subjects with schizophrenia, in parallel with markers for excitatory and inhibitory nerve terminals. The functional implications were also investigated. DESIGN: We used immunocytochemistry to study complexin I and complexin II proteins in hippocampus, as well as the vesicular transporters for gamma-aminobutyric acid (GABA) and for glutamate. Immunocytochemical findings were correlated with cognitive function assessed through medical record review. To further explore the implications of the human findings, we studied rats exposed to haloperidol, amphetamine, and ketamine as well as rats trained in memory tasks. SUBJECTS: We studied hippocampal sections from 12 subjects with schizophrenia and 12 subjects with no known neuropsychiatric disorder. RESULTS: The absolute values and ratio of the hippocampal presynaptic proteins complexin II-complexin I were lower in subjects with schizophrenia. Disturbances in the complexin proteins in subjects with schizophrenia were greater than those observed for vesicular gamma-aminobutyric acid or vesicular glutamate transporters. The lower complexin II-complexin I ratio in several hippocampal subfields in subjects with schizophrenia was inversely correlated with the severity of antemortem cognitive impairment. In contrast, the hippocampal complexin II-complexin I ratio was higher in rats trained in a memory task compared with untrained rats. Treatment of rats with antipsychotic drugs or with the psychotomimetic drugs amphetamine or ketamine did not alter the complexin II-complexin I ratio. CONCLUSIONS: The pathology of hippocampal complexin proteins might play an important role in schizophrenia, especially concerning cognitive disturbances.

Adaptor Proteins, Vesicular Transport↗

PubMed2005

Prenatal ethanol exposure in rats decreases levels of complexin proteins in the frontal cortex.

BACKGROUND: Rodents that are prenatally exposed to ethanol have been shown to exhibit a wide range of cognitive deficits, including impairments in memory, attention and executive function. To determine a potential molecular substrate for cognitive dysfunction in adulthood, we measured regional levels of the presynaptic proteins complexin I and II in a rat model of prenatal ethanol exposure, as levels of these proteins are altered in cognitive-related synaptic plasticity. METHODS: Pregnant female rats received either a liquid ethanol diet (36% ethanol-derived calories) or a liquid control diet (maltose-dextrin isocalorically substituted for ethanol, matched in amount [g/kg body wt/day of gestation] to an ethanol-consuming partner), or were given ad libitum-fed access to standard laboratory chow and water. Levels of complexin I, II and the ubiquitous presynaptic marker synaptophysin were measured in the frontal cortex and hippocampus of adult male offspring, using ELISA. RESULTS: Prenatal exposure to ethanol did not alter levels of presynaptic proteins in the hippocampus or levels of synaptophysin in the prefrontal cortex. However, rats prenatally exposed to ethanol displayed significantly lower levels of both complexin I and II in the prefrontal cortex compared to control animals. CONCLUSIONS: These data indicate that prenatal exposure to ethanol is associated with a selective loss of complexin proteins in the frontal cortex. These proteins are known to be important for activity-dependent neurotransmission, and have previously been shown to mediate synaptic plasticity and cognition. These combined findings suggest that further study of complexin proteins as a substrate for cognitive impairment related to prenatal exposure to ethanol is warranted.

Adaptor Proteins, Vesicular Transport↗

PubMed2005

The genetic and environmental basis of the relationship between schizotypy and personality: a twin study.

The clinical phenotype commonly referred to as schizotypy is used in two different ways in psychiatric practice. One usage emphasizes psychosis-proneness where schizotypy is considered part of the schizophrenia spectrum. The other emphasizes personality aberrations and is classed as a personality disorder. The present study provides evidence that schizotypy is a unitary construct and that features like schizophrenia and personality share a common genetic basis. A sample of 102 monozygotic and 90 dizygotic general population twin pairs completed measures of psychosis-proneness and traits delineating personality disorder. Multivariate genetic analyses showed that the observed relationship between psychotic and personality features is caused almost entirely by common genetic factors. Environmental factors appear to be unique to each measure. On the basis of these findings, it is suggested that the environment mediates change in personality function to psychosis as proposed by Meehl's original concept of schizotaxia.

Adolescent↗

PubMed2005

Reductions in cholesterol and synaptic markers in association cortex in mood disorders.

OBJECTIVES: Cholesterol forms an integral part of cell membranes and is a major component of myelin. Furthermore, cholesterol also plays a vital role in the development, function and stability of synapses. While low serum cholesterol has previously been associated with mood disorders, cholesterol levels have yet to be quantified within the brain in these disorders. The aim of this study was to quantify sterol levels in the brains of patients with major psychiatric disorders and further to relate these levels to markers of myelin and synapses. METHODS: Samples of visual association cortex were obtained postmortem from subjects with bipolar disorder (BPD), major depressive disorder (MDD) and schizophrenia (SCZ) and from controls (all n = 15). Concentrations of brain cholesterol, its precursors lathosterol, desmosterol and lanosterol and its metabolite 24S-hydroxycholesterol were determined by gas-liquid chromatography. Immunoreactivity for myelin basic protein (MBP), synaptophysin and VAMP was quantified by enzyme-linked immunosorbent assay. RESULTS: Cholesterol levels were 13% lower in MDD (p = 0.018) and 10% lower in BPD (p = 0.052) compared with controls. Cholesterol precursor or metabolite concentrations did not differ between groups. Synaptophysin immunoreactivity was 20% lower in BPD (p = 0.025) and VAMP immunoreactivity 37% lower in MDD (p = 0.032) and 45% lower in BPD (p = 0.009). MBP immunoreactivity was not altered in any disorder. CONCLUSIONS: Our data suggest that lower brain cholesterol levels and a reduction in synapses may be features of mood disorders.

Adult↗

PubMed2005

Extrapyramidal symptoms and signs in first-episode, antipsychotic exposed and non-exposed patients with schizophrenia or related psychotic illness.

Movement disorders in first-episode psychosis are increasingly recognized; however, the prevalence and clinical correlates are uncertain. We compared antipsychotic exposed (< 12 weeks) with nonexposed first-episode patients, and report prevalence as well as clinical and demographic variables associated with extrapyramidal dysfunction. Data are baseline assessments from a multicentre, international drug trial of first-episode psychosis (n = 535). Analysis included the Extrapyramidal Symptom Rating Scale, Premorbid Adjustment Scale, and the Positive and Negative Syndrome Scale. Of non-exposed patients, 28.1% (n = 47/167) had at least one mild sign of extrapyramidal dysfunction, as did 46.3% (n = 169/365) of previously exposed patients. Hypokinetic Parkinsonism was the most prevalent disorder. The severity of movement disorders and negative symptoms were correlated; however, the effect sizes were small. Logistic regression analysis indicated that the salient risk factors for all patients were: previous antipsychotic exposure [odds ratio (OR) = 2.4; 95% confidence interval (CI) 1.6-3.6] and poor premorbid functioning (OR = 1.8; 95% CI 1.2-2.6). For the non-exposed group (n = 167), the significant risk factors were: having severe mental illness in the family (OR = 2.9; 95% CI 1.2-7.2) and poor premorbid functioning (OR = 2.3; 95% CI 1.0-5.3). For the previously exposed group (n = 368), the significant variables were: poor premorbid functioning (OR = 1.8; 95%CI 1.2-2.8) and shorter duration of untreated psychosis (OR = 0.78; 95% CI 0.64-0.94). Although antipsychotic exposure was associated with extrapyramidal signs, the results indicate that many first-episode patients with no exposure to antipsychotics also had extrapyramidal dysfunction. In this group, family history and poor premorbid functioning appear to be associated with increased risk for movement disorders.

Adolescent↗