Severity Of Prodromal Symptoms Research Articles

The relationship between prodromal symptom levels and affective temperament features and emotional dysregulation in patients diagnosed with bipolar disorder and their first-degree relatives: A controlled study

BackgroundThe frequency of developing psychiatric symptoms is higher in the first-degree relatives of bipolar patients compared to the healthy population. This study aims to determine the possible diagnosis of bipolarity by revealing the bipolar prodromal features, temperament changes, and emotional disregulation in the first-degree relatives of bipolar patients and their interrelationships. MethodsA total of 150 patients, including bipolar disorder patients, their first-degree relatives, and a healthy control group, aged 18–65 who met the study inclusion criteria, were included in the study. Sociodemographic data form, Bipolar Prodromal Symptom Scale (BPSS), Temperament Evaluation of Memphis, Pisa, Paris, San Diego Autoquestionnaire (TEMPS-A), and Difficulty in Emotion Regulation Scale (DERS) were administered to all participants. ResultsSignificant differences were found between the BPSS, TEMPS-A, and DERS total and subscale scores of the bipolar patient group, first-degree relatives, and healthy control group (p < 0.001). There were significant differences in BPSS frequency and severity subscale scores, TEMPS-A hyperthymic and cyclothymic subscale scores, and DERS strategy, goal-oriented, and awareness subscale scores between patients and their first-degree relatives (p < 0.001). Additionally, all scale scores of the patient relatives were significantly different from the healthy control group (p < 0.001). A significant relationship was found between the prodromal scores and temperament scores of the patient relatives, and between the temperament scores and DERS scores (p < 0.001). ConclusionIt has been observed that the severity and frequency of bipolar prodromal symptoms, temperament changes, and difficulty in mood regulation are higher in bipolar patients and their first-degree relatives compared to the healthy population. Differences were found in hyperthymic and cyclothymic temperament features and difficulty in mood regulation scores between bipolar patients and their first-degree relatives. Patient relatives showed significant changes in all parameters compared to the healthy group. The severity of bipolar prodromal symptoms in patient relatives was associated with cyclothymic and anxious temperament features, while the frequency of bipolar symptoms was associated with anxious temperament. Relationships were found between some temperament and mood regulation difficulty sub-scores. In light of these findings, evaluating clinical variables such as the frequency and severity of prodromal symptoms, temperament features, and difficulty in mood regulation in the first-degree relatives of bipolar patients may be an appropriate approach for diagnosing mood disorders.

Influence of pre-gravid preparation on the course and outcomes of the pregnancy in genital herpes

Introduction. According to researchers from different countries, the incidence of neonatal herpes varies noticeably. Objective. Optimization of pre-gravid preparation of women with chronic recurrent genital herpes to reduce pregnancy complications and improve perinatal outcomes. Мaterials and methods. The study included 58 women with confirmed chronic recurrent genital herpes. Two groups were formed, the main group included 30 women receiving pre-gravid preparation, complex treatment with antiviral and immunomodulatory drugs, the comparison group was represented by 28 women receiving pre-gravid preparation and only antiviral drug. Evaluation of the effectiveness of the treatment of chronic genital herpes and the benefits of pre-gravid preparation were carried out by assessing clinical manifestations, determining the immune status, analyzing the characteristics of the course of pregnancy, childbirth, and perinatal outcomes. Results. As a result of the study, the available data confirm the feasibility of using complex therapy in the treatment of chronic recurrent genital herpes in combination with pre-gravid preparation. Conclusion. Pre-gravid preparation and specific treatment of women with chronic recurrent genital herpes improve the clinical status of patients, increase the interrecurrent period, reduce the severity of prodromal symptoms, the duration and intensity of relapses of the disease, and contribute more favorable course of pregnancy and improvement perinatal outcomes.

Clinical and Functional Differences Between Mexican Youth at Clinical High Risk for Psychosis and With Familial High Risk.

Few studies have explored the differences in clinical psychopathology between youth at high risk for psychosis and those at familial high risk for psychosis. This study seeks to describe and compare the sociodemographic, clinical, and functional characteristics of At-Risk Mental State (ARMS) for psychosis youth and those with a first- or second-degree relative with psychosis (Familial High-Risk: FHR) in a Mexican sample. Twenty-one ARMS individuals and 21 with FHR were evaluated for sociodemographic characteristics, psychopathological symptoms, and functional impairment. ARMS individuals were significantly younger, had fewer years of schooling, and were more likely to be male than those in the FHR group. Groups did not differ as regards marital status or occupation. The ARMS group showed greater severity of prodromal symptoms, schizotypal personality traits, and general psychopathology than the FHR group. In addition, they reported more premorbid adjustment deficit from early adolescence than the FHR group. Current overall social and role functioning was significantly lower in the ARMS group. Findings are consistent with ARMS studies from other countries. First- or second-degree relatives of patients with psychosis should be considered a vulnerable group as they display several symptoms of general psychopathology and may experience social adjustment problems in their adult lives. The lack of early detection and intervention psychosis programs in Mexico underlines the need to prioritize the development of preventive strategies to help close the care gap.

Depression Predicts Global Functional Outcomes in Individuals at Clinical High Risk for Psychosis.

ObjectivesWhile co‐morbid depression is associated with poor functional outcome among patients with schizophrenia, whether depression similarly predicts poorer outcomes in individuals at clinical high‐risk for psychosis (CHR‐P) is not clear. The present study aimed to examine depressive symptoms in relation to long‐term global functional outcomes in the North American Prodrome Longitudinal Study cohort (NAPLS2).MethodsCHR individuals were evaluated clinically at baseline and at 12‐ and 24‐month follow‐ups for depressive and prodromal symptom severity as well as general functioning. Regression models were built to investigate whether baseline positive and depressive symptom scores predicted longitudinal improvement in global functioning.ResultsA total of 406 CHR individuals completed the 12‐month follow‐up assessment and 259 CHR individuals completed the 24‐month assessment. Baseline depressive symptoms in the CHR‐P population were found to predict better global functional outcomes at 2 years. Furthermore, the degree of recovery of depressive symptoms in the first year following baseline completely mediated the association between depressive symptoms at baseline and functional improvement at 2 years.ConclusionsPresence of affective symptoms within the CHR‐P population has different implications for prognosis compared with patients with schizophrenia. The present findings support the view that among those at risk for psychosis, depressive symptoms at baseline predict a more favorable course of functional recovery, and highlight the potential importance of treating co‐occurring depressive symptoms at an early stage of psychosis risk.

GABA levels and TSPO expression in people at clinical high risk for psychosis and healthy volunteers: a PET-MRS study.

γ-Aminobutyric acidergic (GABAergic) dysfunction and immune activation have been implicated in the pathophysiology of schizophrenia. Preclinical evidence suggests that inflammation-related abnormalities may contribute to GABAergic alterations in the brain, but this has never been investigated in vivo in humans. In this multimodal imaging study, we quantified cerebral GABA plus macromolecule (GABA+) levels in antipsychotic-naive people at clinical high risk for psychosis and in healthy volunteers. We investigated for the first time the association between GABA+ levels and expression of translocator protein 18 kDa (TSPO; a marker of microglial activation) using positron emission tomography (PET). Thirty-five people at clinical high risk for psychosis and 18 healthy volunteers underwent 3 T proton magnetic resonance spectroscopy to obtain GABA+ levels in the medial prefrontal cortex (mPFC). A subset (29 people at clinical high risk for psychosis and 15 healthy volunteers) also underwent a high-resolution [18F]FEPPA PET scan to quantify TSPO expression. Each participant was genotyped for the TSPO rs6971 polymorphism. We found that GABA+ levels were significantly associated with TSPO expression in the mPFC (F1,40 = 10.45, p = 0.002). We found no significant differences in GABA+ levels in the mPFC (F1,51 = 0.00, p > 0.99) between people at clinical high risk for psychosis and healthy volunteers. We found no significant correlations between GABA+ levels or residuals of the association with TSPO expression and the severity of prodromal symptoms or cognition. Given the cross-sectional nature of this study, we could determine no cause-and-effect relationships for GABA alterations and TSPO expression. Our findings suggest that TSPO expression is negatively associated with GABA+ levels in the prefrontal cortex, independent of disease status.

Mitochondrial function in individuals at clinical high risk for psychosis

Alterations in mitochondrial function have been implicated in the etiology of schizophrenia. Most studies have investigated alterations in mitochondrial function in patients in which the disorder is already established; however, whether mitochondrial dysfunction predates the onset of psychosis remains unknown. We measured peripheral mitochondrial complex (I–V) function and lactate/pyruvate levels in 27 antipsychotic-naïve individuals at clinical high risk for psychosis (CHR) and 16 healthy controls. We also explored the association between mitochondrial function and brain microglial activation and glutathione levels using a translocator protein 18 kDa [18F]FEPPA PET scan and 1H-MRS scan, respectively. There were no significant differences in mitochondrial complex function and lactate/pyruvate levels between CHR and healthy controls. In the CHR group, mitochondrial complex III function (r = −0.51, p = 0.008) and lactate levels (r = 0.61, p = 0.004) were associated with prodromal negative symptoms. As previously reported, there were no significant differences in microglial activation and glutathione levels between groups, however, mitochondrial complex IV function was inversely related to microglial activation in the hippocampus in CHR (r = −0.42, p = 0.04), but not in healthy controls. In conclusion, alterations in mitochondrial function are not yet evident in CHR, but may relate to the severity of prodromal symptoms, particularly negative symptoms.

26.4 LANGUAGE DISTURBANCE AS A PREDICTOR OF PSYCHOSIS ONSET IN YOUTH AT ENHANCED CLINICAL RISK

BackgroundLanguage offers a privileged view into the mind; it is the basis by which we infer others’ thoughts. Subtle language disturbance is evident in schizophrenia prior to psychosis onset, including decreases in coherence and complexity, as measured using clinical ratings in familial and clinical high-risk (CHR) cohorts. Bearden et al previously used manual linguistic analysis of baseline speech transcripts in CHR to show that illogical and referential thinking, and poverty of content, predict later psychosis onset. Then, Bedi et al used automated natural language processing (NLP) of CHR transcripts to show that decreased semantic coherence and reduction in syntactic complexity predicted psychosis onset. To determine validity and reproducibility, we have applied automated NLP methods, with machine learning, to Bearden’s original CHR transcripts to identify a language profile predictive of psychosis.MethodsParticipants in the Bearden UCLA cohort include 59 CHR, of whom 19 developed psychosis (CHR+) within 2 years, whereas 40 did not (CHR-), as well as 16 recent-onset psychosis and 21 healthy individuals, similar in demographics; speech was elicited using Caplan’s “Story Game. Participants in the Bedi NYC cohort include 34 CHR (29 CHR+), with speech elicited using open-ended interview. Speech was audiotaped, transcribed, de-identified and then subjected to latent semantic analysis to determine coherence and part-of-speech tagging to characterize syntactic structure and complexity. A machine-learning speech classifier of psychosis onset was derived from the UCLA CHR cohort, and then applied both to the NYC CHR cohort and to the UCLA psychosis/control comparison, with convex hull (three-dimension depiction of model) and receiver operating characteristics analyses. Correlational analyses with demographics, symptoms and manual linguistic features were also done.ResultsA four-factor model language classifier derived from the UCLA CHR cohort that comprised three semantic coherence variables and one syntax (usage of possessive pronouns) predicted psychosis t with accuracy of 83% (intra-protocol) for UCLA CHR, 79% (cross-protocol) for NYC CHR, and 72% for discriminating psychosis from normal speech (UCLA psychosis/control). Convex hulls were defined as the smallest space containing all datapoints within a set for CHR- or healthy controls: these convex hulls showed substantial overlap, with CHR+ and psychosis speech datapoints largely outside these convex hulls. Coherence was associated with age, but speech variables did not vary by gender, race, or socioeconomic status in this study. While automated text features were unrelated to prodromal symptom severity, they were highly correlated with manual text features (r = 0.7, p < .000001).DiscussionIn this small preliminary study, we identified and cross-validated a robust language classifier of psychosis risk that comprised measures of semantic coherence (flow of meaning in language) and syntactic usage (usage of possessive pronouns). This classifier had utility in discriminating speech in individuals with recent-onset psychosis from the norm. It demonstrated concurrent validity in that it was highly correlated with manual linguistic features previously identified by Bearden et al, important as automated methods are fast and inexpensive. Automated language features were unrelated to sex, ethnicity or social class in these small samples, and semantic coherence increased with age, consistent with prior studies of normal language development. Of interest, overlapping convex hulls could be defined for groups of individuals without psychosis (UCLA CHR-, NYC CHR- and UCLA healthy), suggesting a constrained hull of normal language in respect to syntax and semantics, from which pre-psychosis and psychosis speech deviates. The RDoC linguistic corpus-based variables of semantic coherence and syntactic structure hold promise as biomarkers of psychosis risk and expression, with initial validation and reproducibility. Next steps in biomarker development include larger multisite studies with standardization of protocols for speech elicitation, test-retest, and attention to traction/feasibility, acceptability, cost, and utility. Mechanistic studies can also yield neural and physiological correlates of abnormal semantic coherence and syntax.

Potentially traumatic events in youth with and at clinical high risk for psychosis.

Previous research has demonstrated a strong association between early trauma exposure and the development of psychotic symptoms. However, few of these studies have included young adolescents and children. This study investigated rates and number of potentially traumatic experiences (PTEs) among typically developing youth (TD; n = 21), youth at clinical high risk for psychosis (CHR; n = 38), and youth with a psychotic disorder (PD; n = 28) between 7 and 18 years of age. CHR participants were further evaluated to determine whether a history of PTEs was associated with prodromal symptom severity. Study group inclusion was determined by structured interviews. Trauma history was assessed using the post-traumatic stress disorder module of the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version. CHR participants with vs without a history of PTEs were compared on severity of prodromal symptoms. CHR and PD participants reported significantly higher rates and numbers of PTEs than TD participants. Contrary to expectations and prior research, CHR participants with vs without a history of PTEs did not differ in prodromal symptom severity. Explanations and implications for the findings are discussed. These findings suggest that the relationship between trauma and the development of psychotic symptoms extends to children and adolescents as young as 7 years of age. This study underscores the importance of screening for trauma exposure among youth seeking treatment for psychotic symptoms.

Family Perception and 6-Month Symptomatic and Functioning Outcomes in Young Adolescents at Clinical High Risk for Psychosis in a General Population in China.

Background and AimsGiven the difficulty of treating schizophrenia and other forms of psychosis, researchers have shifted focus to early detection and intervention of individuals at clinical high risk (CHR) for psychosis. Previous studies have shown that elements in family functioning could predict symptom outcome in CHR individuals. However, associations between self reported family functioning and symptom or functioning outcome of CHR individuals was rarely reported. Our study aimed to investigate the characteristics and the role of family functioning in the development of CHR individuals among young adolescents.MethodsA sample of 32 CHR individuals was recruited from 2800 university students. The characteristics of family perception were evaluated by both Family Assessment Device (FAD) and Family cohesion and adaptability evaluation Scale II (FACES II). 6 month follow up data was available with 25 of the recruited CHR individuals. Baseline socio-demographic characteristics and family functioning were compared between CHR and control group. We also measured the associations between different dimensions of perceived family functioning and both severity of prodromal symptoms and global functioning at baseline and 6-month follow up.ResultsCHR individuals showed more maladaptive family functioning compared to control in nearly all of the dimensions of FAD and FACES II except for Affective Involvement. Better Problem Solving and Affective Responsiveness predicted less severe positive and negative symptoms respectively. Family cohesion and adaptability were not only correlated with the baseline severity of general symptoms, but also positively associated with the general and disorganized symptom outcome.ConclusionsThis study contributed preliminary evidence towards the associations between family perception and symptom outcome of CHR individuals. It also provided evidence for the importance of family interventions on CHR individuals.

Association of Thalamic Dysconnectivity and Conversion to Psychosis in Youth and Young Adults at Elevated Clinical Risk.

Severe neuropsychiatric conditions, such as schizophrenia, affect distributed neural computations. One candidate system profoundly altered in chronic schizophrenia involves the thalamocortical networks. It is widely acknowledged that schizophrenia is a neurodevelopmental disorder that likely affects the brain before onset of clinical symptoms. However, no investigation has tested whether thalamocortical connectivity is altered in individuals at risk for psychosis or whether this pattern is more severe in individuals who later develop full-blown illness. To determine whether baseline thalamocortical connectivity differs between individuals at clinical high risk for psychosis and healthy controls, whether this pattern is more severe in those who later convert to full-blown illness, and whether magnitude of thalamocortical dysconnectivity is associated with baseline prodromal symptom severity. In this multicenter, 2-year follow-up, case-control study, we examined 397 participants aged 12-35 years of age (243 individuals at clinical high risk of psychosis, of whom 21 converted to full-blown illness, and 154 healthy controls). The baseline scan dates were January 15, 2010, to April 30, 2012. Whole-brain thalamic functional connectivity maps were generated using individuals' anatomically defined thalamic seeds, measured using resting-state functional connectivity magnetic resonance imaging. Using baseline magnetic resonance images, we identified thalamocortical dysconnectivity in the 243 individuals at clinical high risk for psychosis, which was particularly pronounced in the 21 participants who converted to full-blown illness. The pattern involved widespread hypoconnectivity between the thalamus and prefrontal and cerebellar areas, which was more prominent in those who converted to full-blown illness (t(173) = 3.77, P < .001, Hedge g = 0.88). Conversely, there was marked thalamic hyperconnectivity with sensory motor areas, again most pronounced in those who converted to full-blown illness (t(173) = 2.85, P < .001, Hedge g = 0.66). Both patterns were significantly correlated with concurrent prodromal symptom severity (r = 0.27, P < 3.6 × 10(-8), Spearman ρ = 0.27, P < 4.75 × 10(-5), 2-tailed). Thalamic dysconnectivity, resembling that seen in schizophrenia, was evident in individuals at clinical high risk for psychosis and more prominently in those who later converted to psychosis. Dysconnectivity correlated with symptom severity, supporting the idea that thalamic connectivity may have prognostic implications for risk of conversion to full-blown illness.

Can age at sexual maturity act as a predictive biomarker for prodromal negative symptoms?

BackgroundPuberty and reproductive hormones have been identified as having a potential role in schizophrenia. Earlier reports have suggested associations between later age at puberty and schizophrenia in males. Similarly, associations have been reported between testosterone levels and psychotic symptoms. In this report, we examined the association between age at puberty and prodromal symptoms of psychosis. Methods58 child or adolescent family members of individuals with schizophrenia were interviewed using the Scale of Prodromal Symptoms and the Tanner Maturational Scale. Age at Tanner pubertal stage was determined and regression analyses were used to explore associations between prodromal symptoms and age at puberty. ResultsAmong males, delayed age at puberty was associated with greater severity of prodromal symptoms; the association between negative prodromal symptoms and delayed age was significant (p=0.001). In females, the association was not statistically significant. ConclusionsOur results suggest that delayed age at puberty may be associated with negative prodromal symptoms of schizophrenia in males. Our findings suggest that delayed age at puberty could potentially be a predictive biomarker for psychopathology in males at risk for schizophrenia.

Prodromal Symptom Severity Predicts Accelerated Gray Matter Reduction and Third Ventricle Expansion among Clinically High-Risk Youth Developing Psychotic Disorders

A recent prospective longitudinal neuroimaging study of 274 prodromal risk syndrome subjects revealed that those who later developed full-blown psychotic symptoms had exhibited accelerated gray matter loss and third ventricle expansion around the time of psychosis onset. Previous studies also indicate that higher levels of unusual thought content during prodromal states are a significant predictor of psychosis in clinically high-risk (CHR) youth. However, the relationship between clinical symptoms and changes in neuroanatomical structure has not been previously examined in the North American Prodrome Longitudinal Study (NAPLS) sample at the whole-brain level. In this report, we investigated whether symptom severity as measured by the Scale of Prodromal Symptoms (SOPS) predicted the accelerated gray matter decline in 274 CHR cases, including 35 who converted to psychosis. Higher levels of unusual thought content at baseline were associated with a steeper rate of gray matter loss in the prefrontal cortex bilaterally among converters. In contrast, there was no association found among nonconverters. Steeper gray matter loss seems to be unique to those (CHR) individuals with higher levels of subpsychotic predelusional symptoms that acutely worsen in the ramp-up to full-blown psychosis, and as such may reflect pathophysiological processes driving the emergence of psychosis.

Gray matter loss in young relatives at risk for schizophrenia: Relation with prodromal psychopathology

The maturation of neocortical regions mediating social cognition during adolescence and young adulthood in relatives of schizophrenia patients may be vulnerable to heritable alterations of neurodevelopment. Prodromal psychotic symptoms, commonly emerging during this period in relatives, have been hypothesized to result from alterations in brain regions mediating social cognition. We hypothesized these regions to show longitudinal alterations and these alterations to predict prodromal symptoms in adolescent and young adult relatives of schizophrenia patients. 27 Healthy controls and 23 relatives were assessed at baseline and one-year follow-up using scale of prodromal symptoms and gray matter volumes of hypothesized regions from T1-MRI images. Regional volumes showing deficits on ANCOVA and repeated-measures ANCOVAs (controlling intra cranial volume, age and gender) were correlated with prodromal symptoms. At baseline, bilateral amygdalae, bilateral pars triangulares, left lateral orbitofrontal, right frontal pole, angular and supramarginal gyrii were smaller in relatives compared to controls. Relatives declined but controls increased or remained stable on bilateral lateral orbitofrontal, left rostral anterior cingulate, left medial prefrontal, right inferior frontal gyrus and left temporal pole volumes at follow-up relative to baseline. Smaller volumes predicted greater severity of prodromal symptoms at both cross-sectional assessments. Longitudinally, smaller baseline volumes predicted greater prodromal symptoms at follow-up; greater longitudinal decreases in volumes predicted worsening (increase) of prodromal symptoms over time. These preliminary findings suggest that abnormal longitudinal gray matter loss may occur in regions mediating social cognition and may convey risk for prodromal symptoms during adolescence and early adulthood in individuals with a familial diathesis for schizophrenia.

Predicting the longitudinal effects of the family environment on prodromal symptoms and functioning in patients at-risk for psychosis

The current study examined the relationship between the family environment and symptoms and functioning over time in a group of adolescents and young adults at clinical high risk for psychosis (N=63). The current study compared the ability of interview-based versus self-report ratings of the family environment to predict the severity of prodromal symptoms and functioning over time. The family environmental factors were measured by interviewer ratings of the Camberwell Family Interview (CFI), self-report questionnaires surveying the patient's perceptions of criticism and warmth, and parent reported perceptions of their own level of criticism and warmth. Patients living in a critical family environment, as measured by the CFI at baseline, exhibited significantly worse positive symptoms at a 6-month follow-up, relative to patients living in a low-key family environment. In terms of protective effects, warmth and an optimal level of family involvement interacted such that the two jointly predicted improved functioning at the 6-month follow-up. Overall, both interview-based and self-report ratings of the family environment were predictive of symptoms and functioning at follow-up; however patient's self-report ratings of criticism had stronger predictive power. These results suggest that the family environment should be a specific target of treatment for individuals at risk for psychosis.

The Reliability and Validity of the Korean Version of the Structured Interview for Prodromal Syndrome

ObjectiveThe Structured Interview for Prodromal Syndrome (SIPS) from Yale University is intended to diagnose prodromal syndrome of psychosis and to measure the severity of prodromal symptoms. Here, a Korean version of SIPS is presented, and its reliability, validity, and factor structures are examined using a representative Korean sample.MethodsThe Korean version of SIPS was administered to 40 participants over a period of 1 year. The inter-rater reliability and internal consistency of the SIPS were then evaluated. In addition, its factor structure was investigated using principal-axis factor analysis. Concurrent validity was explored using Pearson correlation coefficients with the Positive and Negative Syndrome Scale (PANSS).ResultsOf the 40 subjects, 12.5% developed psychotic disorders during the 1-year follow-up period. Inter-rater reliability was good (intra-class correlations=0.96), and internal consistency was acceptable (Cronbach's alpha=0.83). A three-factor resolution displayed the best simple structure and accounted for 52.6% of all item variance. Factors 1 and 2 showed strong correlations with negative symptoms and cognitive dysfunction, respectively, on the PANSS. Factor 3 was not correlated with any factor on the PANSS.ConclusionThe Korean version of SIPS is a reliable instrument for the assessment of prodromal symptoms in subjects and may be used to evaluate prodromal psychosis.

The relation of antipsychotic and antidepressant medication with baseline symptoms and symptom progression: A naturalistic study of the North American Prodrome Longitudinal Sample

A substantial number of patients who meet criteria for a prodromal syndrome for first psychosis are treated with antipsychotic and/or antidepressant medications. There is suggestive evidence that both classes of medication may reduce prodromal symptoms. This longitudinal study examined the relation of antipsychotic and antidepressant medication with prodromal symptom severity at baseline and 6-month follow-up. Participants met Structured Interview for Prodromal Syndromes (SIPS) criteria for the prodrome, and were evaluated at eight centers as part of the North American Prodrome Longitudinal Study (NAPLS). Symptom ratings (positive, negative, disorganized and general) and data on antipsychotics, SSRIs, and other antidepressant medications were obtained at baseline and 6-month follow-up. Analyses revealed that all symptom dimensions declined in severity over time, but there were differences in the magnitude of the decline as a function of antipsychotic medication. Those never on antipsychotics showed less reduction in positive and disorganized symptoms over time. SSRIs and other antidepressants were not linked with declines in symptom severity. Consistent with findings from small-sample, clinical trials, the present results suggest that atypical antipsychotics may be effective in reducing the severity of attenuated positive symptoms associated with the prodrome to psychotic disorders. Limitations of the present study are noted, including the fact that it is not a randomized trial, and data on duration and dosage of medication and 2-year follow-up were not available for most participants. The results are discussed in light of the relative risks and benefits of preventive interventions, both medication and cognitive therapies, and the importance of future clinical trials.

The assessment of "prodromal schizophrenia": unresolved issues and future directions.

Because of the novelty of research with clinical high risk ("prodromal") patients, many unresolved issues exist concerning how the prodromal state is defined and measured. Data are presented from the Recognition and Prevention (RAP) program at the Zucker Hillside Hospital to address several outstanding questions. Baseline attenuated positive symptoms were rated in 42 putatively prodromal patients in the RAP program using the Scale of Prodromal Symptoms (SOPS). Followup data of 6 months or more were available on 34 of these subjects; 9 of these (26.5%) developed psychotic disorders. Patients who developed psychosis had significantly higher SOPS positive symptom scores at baseline than those who did not. Various thresholds, using both total SOPS positive symptom scores and highest single item score, significantly predicted transition to psychosis, which calls into question appropriate cutoffs for the distinction between health, prodromal status, and psychosis. The SOPS positive symptom "conceptual disorganization" was found to be significantly related to disorganized behavior but not to other positive symptoms or to psychotic outcome, suggesting the importance of examining dimensions of psychopathology. The dimensional quantification of prodromal symptom severity may be an important direction for future studies of the assessment of at-risk states.

Acute poliomyelitis: A clinical and statistical study of 263 cases

Poliomyelitis knows no limitation of age, sex, or race. The term “infantile paralysis” should be discarded in the light of present knowledge. Increased physician awareness of the disease and more frequent recourse to lumbar puncture in suspected cases have contributed to the apparent increase in incidence of the disease as well as to its shift toward older age groups. We have reported on our experiencesin the 1950 epidemic and have reviewed 263 cases studied at the height of the epidemic. More than 25 per cent of our cases were nonparalytic, 22.7 per cent were of the bulbar type, and 50.4 per cent were spinal in type. The over-all mortality rate was 8 per cent. Symptomatology, age and sex ratios, and mortality figures were in general agreement with those reported in other epidemics. Study of the spinal fluid findings offered no prognostic guide to the extent of paralytic involvement. It assumed only a diagnostic confirmatory role in most instances. About 5 per cent of patients showed no pleocytosis or increased spinal fluid protein values on hospital admission. Similarly the length or severity of prodromal symptoms had no bearing on the ultimate outcome of the disease. The virulence of the disease variedfrom month to month and was emphasized. A general plan of treatment of the major types of the disease was given. The cause of death in poliomyelitiswas generally the result of bulbar involvement. The exact mechanism is controversial. We have emphasized the importance of pulmonary angiospasm and have offered this as an explanation for the underlying cause of death. Tracheotomy is of value only when there is tracheobronchial obstruction. This is generally not present in bulbar poliomyelitis. In addition the use of vasodilator drugs, notably Priscoline, has been cited in the treatment of vasospastic phenomena in poliomyelitis. Poliomyelitis knows no limitation of age, sex, or race. The term “infantile paralysis” should be discarded in the light of present knowledge. Increased physician awareness of the disease and more frequent recourse to lumbar puncture in suspected cases have contributed to the apparent increase in incidence of the disease as well as to its shift toward older age groups. We have reported on our experiencesin the 1950 epidemic and have reviewed 263 cases studied at the height of the epidemic. More than 25 per cent of our cases were nonparalytic, 22.7 per cent were of the bulbar type, and 50.4 per cent were spinal in type. The over-all mortality rate was 8 per cent. Symptomatology, age and sex ratios, and mortality figures were in general agreement with those reported in other epidemics. Study of the spinal fluid findings offered no prognostic guide to the extent of paralytic involvement. It assumed only a diagnostic confirmatory role in most instances. About 5 per cent of patients showed no pleocytosis or increased spinal fluid protein values on hospital admission. Similarly the length or severity of prodromal symptoms had no bearing on the ultimate outcome of the disease. The virulence of the disease variedfrom month to month and was emphasized. A general plan of treatment of the major types of the disease was given. The cause of death in poliomyelitiswas generally the result of bulbar involvement. The exact mechanism is controversial. We have emphasized the importance of pulmonary angiospasm and have offered this as an explanation for the underlying cause of death. Tracheotomy is of value only when there is tracheobronchial obstruction. This is generally not present in bulbar poliomyelitis. In addition the use of vasodilator drugs, notably Priscoline, has been cited in the treatment of vasospastic phenomena in poliomyelitis.