Discriminating value of total minor physical anomaly score on the Waldrop physical anomaly scale between schizophrenia patients and normal control subjects

Minor physical anomalies (MPAs) are slight structural aberrations that are believed to be associated with abnormal neurodevelopment. Studies of schizophrenia patients show that these patients score higher in MPAs than normal controls. The present study attempted to assess the potential value of MPAs as a classifying test in the status schizophrenia patient versus normal control. Seventy-six schizophrenia patients and 82 normal controls were assessed for MPAs using the Waldrop Physical Anomaly Scale, and specificity, sensitivity, and predictive value of the total MPA score were determined. A significantly higher percentage of schizophrenia patients than normal controls had high numbers of MPAs. Total MPA scores higher than 4 showed the most balanced set of sensitivity (76.3%), specificity (72.0%), and positive (71.6%) and negative (76.6%) predictive values for schizophrenia and were the cutoff scores that optimally discriminate schizophrenia patients from normal controls. Schizophrenia patients showed a higher percentage of subjects with prominent MPA scores. The results are consistent with the hypothesis that MPAs might reflect extragenetic stressful events and present total MPA score as a reliable index in distinguishing between schizophrenia patients and normal controls.     

Faisabilité de l'autoévaluation dans le dépistage de l'hypomanie

The Hypomania Checklist (HC) is a 20-item questionnaire, which is easy to fill in and designed to help clinicians collect data for diagnosing bipolar disorder. This tool could be very useful in primary care where type II bipolar disorder is under-diagnosed, however, to date no suitable cut-off score correlating with a high probability of bipolar II disorder diagnosis has yet been validated.

Method

In a French clinico-epidemiological multi-center survey (EPIDEP) a national sample of patients with DSM-IV major depressive episode (MDE) was recruited and assessed at admittance and four weeks later. Diagnoses of unipolar or bipolar disorder were made according to a semi-structured interview adapted from the DSM-IV. In addition, the HC and questionnaires on affective temperament were administered at the second interview. In the analyses, the diagnostic accuracy was computed in terms of sensitivity, specificity, predictive positive value and predictive negative value, by varying cut-off scores on the HC. The Receiver Operating Characteristic (ROC) statistical technique was used to compare the diagnostic value of HC with the semi-structured interview adapted from the DSM-IV.

Results

Of the 493 patients with a MDE DSM-IV diagnosis, 468 filled in the HC, from which the six following groups were formed: strict unipolar disorder (UP, N = 201), bipolar I disorder (BP-I, n=39), bipolar II disorder (BP-II, N = 141), patients with mania or hypomania secondary to an antidepressant treatment (N = 51), cyclothymia (N = 14) and hyperthymia (N = 22). Comparing the BP-II patient group (N = 141) with the strict UP group (N = 201) the most discriminating HC score was 9, which identified 81% of patients correctly, with a sensitivity of 86.5, a specificity of 77.1, a predictive positive value of 72.6 and a predictive negative value of 89.1. Some cases identified as cyclothymic and hyperthymic temperaments by the affective temperament questionnaire but meeting DSM-IV criteria for major depressive disorder were included in the unipolar group (N = 237). The same score of 9 was validated, identifying a percentage of patients with correct diagnosis of unipolar depression of 78.3%, a sensitivity of 86.5, a specificity of 73.4, a predictive positive value of 66.0 and a predictive negative value of 90.1. If patients with mania or hypomania secondary to an antidepressant treatment were included as a subgroup of BP-II, a score of ten appeared as the most relevant, with a percentage of patients with correct diagnosis of 79.0 %, a sensitivity of 80.2, a specificity of 78.1, a predictive positive value of 74.8 and a predictive negative value of 83.0. ROC curves confirmed these values. Lastly when BP-I patients (N = 39) were compared to the strict UP group (N = 201) the most discriminating HC score was 11, with a percentage of patients with correct diagnosis of 86.3%, a sensitivity of 74.4, a specificity of 88.6, a predictive positive value of 55.8 and a predictive negative value of 94.7, but the BP-I group was too small to validate the score of 11.

Conclusions

These results indicate that a score of 9 on the HC is highly correlated with a BP-II diagnosis (and a score of 10 if patients with mania induced by antidepressants are considered as BP-II), and suggest that a wider use of the HC in primary care associated with strong GP/Psychiatrist networks could improve the detection, and with appropriate treatment, the prognosis of Bipolar II disorder.     

Minor physical anomalies in schizophrenia and bipolar affective disorder.

OBJECTIVE: The prevalence of minor physical anomalies (MPAs) (prenatal errors of morphogenesis) was evaluated in patients with schizophrenia and bipolar affective disorder. METHOD: A new modification of the Waldrop-scale was used to detect the presence or absence of 57 MPAs in 30 patients with schizophrenia, 30 with bipolar disorder, and in 30 matched normal controls. RESULTS: Patients with schizophrenia compared to normal controls had significantly higher rates of three minor malformations (furrowed tongue, flat occiput, primitive shape of ears) and those of one phenogenetic variant (wide distance between toes 1 and 2), and they also had a significantly higher rate of one minor malformation (primitive shape of ears), as compared to patients with bipolar disorder. In patients with bipolar disorder, furrowed tongue was significantly more common than in controls. CONCLUSIONS: These results support an 'early' neuro-developmental model of schizophrenia.     

Performance of the Bipolar Spectrum Diagnostic Scale in psychiatric outpatients

Zimmerman M, Galione JN, Chelminski I, Young D, Ruggero CJ. Performance of the Bipolar Spectrum Diagnostic Scale in psychiatric outpatients.
Bipolar Disord 2010: 12: 528–538. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S. Objectives: Recent research has suggested that bipolar disorder, when defined to include milder variants such as bipolar II disorder and bipolar disorder not otherwise specified (NOS), is more prevalent than had been previously reported and often underrecognized. Recommendations for improving the detection of bipolar disorder have included careful clinical evaluations inquiring about a history of mania and hypomania and the use of screening questionnaires. The Bipolar Spectrum Diagnostic Scale (BSDS) was designed to be particularly sensitive to the milder variants of bipolar disorder. In the present report from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project, we examined the operating characteristics of the BSDS in a large sample of psychiatric outpatients presenting for treatment. Methods: A total of 1,100 psychiatric outpatients were interviewed with the Structured Clinical Interview for DSM‐IV and asked to complete the BSDS. Missing data on the BSDS reduced the sample size to 961, approximately 10% (n = 90) of whom were diagnosed with bipolar disorder. Results: The sensitivity of the BSDS was similar for bipolar I disorder, bipolar II disorder, and bipolar disorder NOS/cyclothymia. A receiver operating curve (ROC) analysis indicated that cutoffs of 11 and 12 maximized the sum of sensitivity and specificity for the entire group of patients with bipolar disorder (area under curve = 0.80, p < 0.001). The cutoff point associated with 90% sensitivity for the entire sample of patients with bipolar disorder was 8. At this cutoff the specificity of the scale was 51.1% and positive predictive value was 16.0%. We compared the patients with and without bipolar disorder on each of the BSDS symptom items. The odds ratios were higher for the items assessing hypomanic/manic symptoms than items assessing depressive symptoms. We therefore examined the performance of a subscale composed only of the hypomania/mania items. The area under the curve in the ROC analysis was nearly identical to that of the entire scale (0.81, p < 0.001). Conclusions: With its high negative predictive value, the BSDS was excellent at ruling out a diagnosis of bipolar disorder; however, the low positive predictive value indicates that it is not good at ruling in the diagnosis. These data raise questions about the use of the BSDS as a screening measure in routine clinical psychiatric practice.     

探索性眼球运动检查在精神分裂症诊断中的价值

目的 探讨探索性眼球活动测验在精神分裂症诊断中的价值。方法 对61名精神分裂症患者和56名正常对照进行了探索性眼球活动检查。记录凝视点数(NEF)和反应性探索分(RSS)；计算敏感度、特异度、阳性预测值。结果 精神分裂症患者的NEF和RSS均显著低于正常对照。NEF和RSS的敏感度、特异度、阳性预测值较好。结论 探索性眼球活动测验在精神分裂症诊断中有一定的辅助价值。     

基于扩散张量成像的双相障碍Ⅰ型患者全脑白质完整性研究

目的比较双相情感障碍(BD)Ⅰ型患者和健康对照组脑白质部分各向异性分数(FA),探索BD-Ⅰ型患者的脑白质完整性。方法 2012年1月-2014年7月于中南大学湘雅二医院纳入符合《精神障碍诊断与统计手册(第4版)》(DSM-Ⅳ)诊断标准的BD-Ⅰ型患者22例为患者组,同期在中南大学湘雅二医院周边社区招募性别、年龄及受教育年限与患者组匹配的24名健康者为对照组。采用3.0T磁共振成像系统采集所有被试的脑白质结构相数据,使用FSL、SPM完成FA参数图计算、空间标准化、高斯平滑,采用两独立样本t检验分析患者组与对照组FA值差异有统计学意义的脑区。结果与对照组相比,患者组FA值增高的脑区为右侧小脑后叶(P0.01),降低的脑区包括颞上回、小脑前叶、左侧岛叶和左侧尾状核(P均0.01)。结论 BD-Ⅰ型患者白质完整性受损,边缘系统、颞叶和小脑白质完整性受损可能与BD-Ⅰ型的病理生理学机制有关。     

Measuring depressive symptoms among treatment-resistant seizure disorder patients: POMS Depression scale as an alternative to the BDI-II

Major depressive disorder (MDD) is the most prevalent psychiatric comorbidity among patients with treatment-resistant seizures. The Beck Depression Inventory-II (BDI-II) is often used to measure the severity of self-reported depressive symptoms among patients with seizure disorders. In contrast, researchers often use the Profile of Mood States (POMS) Depression (D) scale to assess depressed mood among other medical patient groups. The clinical significance of POMS-D scores among seizure disorder patients is not clear. In this study, we computed the correlation of POMS-D and BDI-II scores, determined a formula for converting POMS-D scores to BDI-II scores, and computed the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the POMS-D among seizure disorder patients. Two BDI-II cutoffs (BDI-II16 and 20) were used as criteria for significant reported depressive symptoms. We found a strong correlation between POMS-D and BDI-II scores. Analyses indicated that POMS-D scores strongly predict BDI-II scores. In addition, the sensitivity, specificity, PPV, and NPV values obtained demonstrated that POMS-D scores accurately classify seizure disorder patients who endorse significant depressive symptoms. These results suggest that the POMS-D may be effective in measuring reported depressive symptoms among seizure disorder patients.     

Performance of the mood disorders questionnaire in a psychiatric outpatient setting

Objectives:  The Mood Disorders Questionnaire (MDQ) has been the most widely studied screening questionnaire for bipolar disorder, though few studies have examined its performance in a heterogeneous sample of psychiatric outpatients. In the present report from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project, we examined the operating characteristics of the MDQ in a large sample of psychiatric outpatients presenting for treatment.
Methods:  A total of 534 psychiatric outpatients were interviewed with the Structured Clinical Interview for DSM-IV and asked to complete the MDQ. Missing data on the MDQ reduced the number of patients to 480, 10.4% (n = 52) of whom were diagnosed with bipolar disorder.
Results:  Based on the scoring guidelines recommended by the developers of the MDQ, the sensitivity of the scale was only 63.5% for the entire group of bipolar patients. The specificity of the scale was 84.8%, and the positive and negative predictive values were 33.7% and 95.0%, respectively. When impairment was not required to define a case on the MDQ, then sensitivity increased to 75.0%, specificity dropped to 78.5%, positive predictive value was 29.8%, and negative predictive value was 96.3%.
Conclusions:  In a large sample of psychiatric outpatients, we found that the MDQ, when scored according to the developers' recommendations, had inadequate sensitivity as a screening measure. After the threshold to determine MDQ caseness was lowered by not requiring moderate or severe impairment, the sensitivity of the scale increased, but specificity decreased, and positive predictive value remained below 30%. These results raise questions regarding the MDQ's utility in routine clinical practice.     

The mistaken claim of bipolar ‘overdiagnosis’: solving the false positives problem for DSM‐5/ICD‐11

Phelps J, Ghaemi SN. The mistaken claim of bipolar ‘overdiagnosis’: solving the false positives problem for DSM‐5/ICD‐11. Objective: For psychiatric diagnoses, solving the problem of false positives is thought to be a matter of tightening diagnostic criteria. But low prevalence illnesses by their nature have high false positive rates. A recent study of bipolar disorder found the predictive value of bipolar diagnoses to be <50%. Is it possible to achieve much higher diagnostic accuracy for psychiatric diagnoses? Method: We calculate predictive values while varying diagnostic sensitivity and holding specificity constant, and vice versa, for a given prevalence of illness. We then calculate predictive values while holding sensitivity and specificity constant, but varying prior probability (clinically feasible by assessing other factors associated with bipolar outcomes, such as family history and degree of recurrence). Results: Assuming a sample in which the prevalence of illness is 10%, achieving positive predictive values (PPV) >50% requires diagnostic specificity of >95%. Holding specificity at a level already achieved clinically (86%), increasing prior probability yields predictive values as high as 83%. Conclusion: Systematic assessment of clinical factors that increase the prior probability of illness, before applying DSM/ICD criteria, could raise PPV substantially compared with targeting greater specificity via more stringent diagnostic criteria.     

Affective dimensions as a diagnostic tool for bipolar disorder in first psychotic episodes

ObjectiveTo examine the predictive diagnostic value of affective symptomatology in a first-episode psychosis (FEP) sample with 5 years’ follow-up.MethodAffective dimensions (depressive, manic, activation, dysphoric) were measured at baseline and 5 years in 112 FEP patients based on a factor structure analysis using the Young Mania Rating Scale and Hamilton Depression Rating Scale. Patients were classified as having a diagnosis of bipolar disorder at baseline (BDi), bipolar disorder at 5 years (BDf), or “other psychosis”. The ability of affective dimensions to discriminate between these diagnostic groups and to predict a bipolar disorder diagnosis was analysed.ResultsManic dimension score was higher in BDi vs. BDf, and both groups had higher manic and activation scores vs. “other psychosis”. Activation dimension predicted a bipolar diagnosis at 5 years (odds ratio = 1.383; 95% confidence interval, 1.205–1.587; P = 0.000), and showed high levels of sensitivity (86.2%), specificity (71.7%), positive (57.8%) and negative predictive value (90.5%). Absence of the manic dimension and presence of the depressive dimension were both significant predictors of an early misdiagnosis.ConclusionThe activation dimension is a diagnostic predictor for bipolar disorder in FEP. The manic dimension contributes to a bipolar diagnosis and its absence can lead to early misdiagnosis.     

Detecting Attention Deficit Hyperactivity Disorder in a Communications Clinic: Diagnostic Utility of the Gordon Diagnostic System

This study examines the sensitivity, specificity, predictive values, and likelihood ratios of laboratory measures of attention and impulsivity (the Gordon Diagnostic System; GDS) in 99 school-aged boys with a history of suspected language disorders. Classification analyses comparing scores from these tests with parent and teacher ratings of attention deficit hyperactivity disorder (ADHD) symptoms revealed low positive predictive values (20.0% to 36.8%) and high negative predictive values (71.9% to 87.9%). Likelihood ratios for abnormal test scores were low to moderate (0.74 to 1.73), suggesting that these tests may not accurately identify children with ADHD. Likelihood ratios for normal scores were also low to moderate (0.41 to 1.16). These findings suggest that GDS scores have clinical utility in ruling out a diagnosis of ADHD, but not in confirming the diagnosis in a clinic population of boys with communicative disorders who are at risk for developing ADHD.     

Detecting Attention Deficit Hyperactivity Disorder in a communications clinic: diagnostic utility of the Gordon Diagnostic System

This study examines the sensitivity, specificity, predictive values, and likelihood ratios of laboratory measures of attention and impulsivity (the Gordon Diagnostic System; GDS) in 99 school-aged boys with a history of suspected language disorders. Classification analyses comparing scores from these tests with parent and teacher ratings of attention deficit hyperactivity disorder (ADHD) symptoms revealed low positive predictive values (20.0% to 36.8%) and high negative predictive values (71.9% to 87.9%). Likelihood ratios for abnormal test scores were low to moderate (0.74 to 1.73), suggesting that these tests may not accurately identify children with ADHD. Likelihood ratios for normal scores were also low to moderate (0.41 to 1.16). These findings suggest that GDS scores have clinical utility in ruling out a diagnosis of ADHD, but not in confirming the diagnosis in a clinic population of boys with communicative disorders who are at risk for developing ADHD.     

Resting energy expenditure in manic episode

Objective:  We aimed to assess the resting energy expenditure in bipolar I disorder, manic episode patients.
Method:  Forty-two bipolar I disorder, manic episode patients that were treated in the inpatient psychiatry clinic of Trakya University Hospital and had met the necessary study criteria were included along with 27 controls. DSM-IV criteria and the Bech-Rafaelsen Mania Rating Scale were used to evaluate patients' diagnosis and severity of the manic episodes. The indirect calorimetry device was used to measure resting energy expenditure values.
Results:  Resting energy expenditure values of manic patients were found to be higher than those of the controls. Controls showed significant correlations between body mass index and resting energy expenditure, but manic patients did not exhibit similar correlations. There was also no relation between Bech-Rafaelsen Mania Rating Scale scores and resting energy expenditure values in manic patients.
Conclusions:  We found significantly increased resting energy expenditure values in bipolar I disorder, manic episode patients. These findings suggest a possible clinical use of resting energy expenditure for evaluation of bipolar I disorder manic episode and also suggest resting energy expenditure as a possible biological marker.     

双极性指数对双相障碍的识别效能

目的:探讨双极性指数(bipolarity index,BPX)对双相障碍(BD)的识别效能。方法:对经简明国际神经精神访谈(MINI)、符合美国精神障碍诊断与统计手册第4版(DSM-IV)BD及复发性抑郁症(RMDD)诊断标准的住院患者各60例进行BPX评估表评估,BPX总分包含躁狂发作特征、发病年龄、病程/相关特征、治疗反应及家族史5个维度。结果:BD组BPX为35~95分,平均(67.4±13.0)分;RMDD组为7~27分,平均(15.3±4.1)分;BD组BPX评分显著高于RMDD组(P0.05)。以BPX 44分为分界值,筛查BD的灵敏度为93.7%,特异度为100%,漏诊率为6.3%,阴性预测值93.7%;以BPX38.5分为界值分,筛查BD的灵敏度为98.3%,特异度为100%,漏诊率为1.7%,阴性预测值98.3%。RMDD组没有1例≥38.5分。BD组和RMDD组BPX评分均与首发年龄、治疗反应呈正相关(P均0.01);BD组BPX评分亦与文化程度及家族史呈正相关(P均0.05)。结论:应用BPX筛检BD具有较高的灵敏度和特异度。有家族史、发作频繁、首次发作年龄小的患者BPX评分高。     

Predictive values of motor unit potential analysis in limb muscles

ObjectiveIn interpretation of diagnostic findings the probability that an abnormal test accurately indicates pathology (i.e., the positive predictive value), and a normal test accurately excludes pathology (i.e., the negative predictive value) is the most important. For motor unit potential (MUP) analysis no such data has been published; hence this was the aim of this study.MethodsIn 31 patients with facioscapulohumeral muscular dystrophy (FSHD) and 34 controls the biceps brachii and vastus lateralis muscles were examined by concentric needle electromyography (EMG), using template operated MUP analysis. These results were compared to non-parametric reference data obtained in another group of 34 (biceps brachii) and 46 (vastus lateralis) control subjects.ResultsFor the biceps brachii muscles sensitivity was 59%, specificity 91%, the positive predictive value 85%, and negative predictive value 72% with at least two criteria (mean values or outliers for MUP thickness, amplitude and duration) below the reference intervals. In addition, all subjects with three abnormal EMG criteria were FSHD patients, and 90% of subjects with normal EMG were controls.ConclusionsTemplate operated MUP analysis demonstrated reasonable predictive value for diagnosis and exclusion of myopathy.SignificanceQuantitative MUP analysis seems to be useful for the preliminary diagnosis of FSHD in patients with appropriate clinical picture.     

The spectrum of substance abuse in bipolar disorder: reasons for use, sensation seeking and substance sensitivity

OBJECTIVES: To examine the spectrum of alcohol and substance abuse, including reasons for use, in patients with bipolar I disorder, compared with patients with substance use disorder and healthy controls, with a specific focus on the relationship between substance use, substance sensitivity, other comorbid psychiatric symptoms and traits related to sensation seeking. METHODS: This study included 104 patients with bipolar I disorder (BPD I), of whom 57 (54.8%) met DSM-IV criteria for lifetime alcohol or substance use disorder (BPD + SUD), 35 patients with substance use disorder (SUD) and no psychiatric disorder and 50 healthy controls. Assessments included the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID) and the Structured Clinical Interview for the Spectrum of Substance Use (SCI-SUBS). RESULTS: Patients with BPD + SUD and SUD had significantly higher scores on the SCI-SUBS domains of self-medication, substance sensitivity and sensation seeking compared with patients with BPD and healthy controls. Reasons for substance use did not differ between patients with BPD + SUD and patients with SUD. Those most frequently cited were: improving mood; relieving tension; alleviating boredom; achieving/maintaining euphoria; and increasing energy. CONCLUSIONS: Recourse to substances is associated with increased mood and anxiety symptoms, substance sensitivity, and sensation seeking among patients with BPD + SUD and SUD. Substance sensitivity and sensation seeking traits should be investigated in all patients with BPD as possible factors associated with a development of SUD, in order to warn patients of the specific risks related to improper use of medications and substances.     

Are screening scales for bipolar disorder good enough to be used in clinical practice?

Bipolar disorder is often underdiagnosed. Recommendations for improving the detection of bipolar disorder include the use of screening questionnaires. The most widely studied screening scale is the Mood Disorders Questionnaire (MDQ). Studies of the performance of the MDQ in heterogeneous samples of psychiatric outpatients presenting for treatment have raised concerns about the adequacy of the MDQ as a screening measure because of its relatively low sensitivity. The sensitivity of a scale is not an inherent property of the instrument but depends on the threshold used to identify positive cases. Prior studies used the scoring recommendations of the developers of the MDQ to examine its performance; none examined the performance of the scale across the range of cutoff scores to determine whether a lower threshold would be more appropriate for the purposes of screening. The goal of the present study was to examine the operating characteristics of the MDQ at all cutoff scores to determine the cutoff point that would be appropriate for the purpose of screening. Seven hundred fifty-two psychiatric outpatients were interviewed with the Structured Clinical Interview for DSM-IV, and completed the MDQ. When MDQ caseness was based only on symptom score without regard to level of impairment, the cutoff score associated with at least 90% sensitivity was 5. At this cutoff the specificity of the MDQ was 60.7%, and its positive predictive value was 22.1%. These findings indicate that when the cutoff to identify cases on the MDQ was set to achieve a desired level of sensitivity as a screening instrument most cases screening positive on the scale did not have bipolar disorder. Low positive predictive value does not support the use of the MDQ or any bipolar disorder screening scale in psychiatric clinical practice.     

Executive functioning in familial bipolar I disorder patients and their unaffected relatives

Schulze KK, Walshe M, Stahl D, Hall MH, Kravariti E, Morris R, Marshall N, McDonald C, Murray RM, Bramon E. Executive functioning in familial bipolar I disorder patients and their unaffected relatives.
Bipolar Disord 2011: 13: 208–216. © 2011 The Authors.
Journal compilation © 2011 John Wiley & Sons A/S. Objective: To compare the executive function of patients with familial bipolar I disorder (BP‐I) with a history of psychotic symptoms to their first‐degree relatives and normal controls. Methods: Three domains of executive function: response inhibition, working memory, and cognitive set shifting were assessed in 44 familial patients with a lifetime diagnosis of BP‐I who had experienced psychotic symptoms, 42 of their unaffected first‐degree relatives, and 47 controls. Results: Bipolar disorder patients and their unaffected relatives had significantly worse scores for response inhibition compared to healthy controls. The groups did not differ in working memory or cognitive set shifting. Conclusions: Impairments in response inhibition are associated with both psychotic bipolar disorder and genetic liability for this illness. Our results indicate that deficits in this specific domain of executive functioning are a promising candidate endophenotype for psychotic bipolar disorder.     

Trait impulsivity and increased pre-attentional sensitivity to intense stimuli in bipolar disorder and controls

Impulsivity and sensation seeking are stimulus-oriented traits. Because they differ in degree of intention and planning, they may have distinct neurophysiological mechanisms. Impulsivity is prominent in bipolar disorder, and may be related to pre-attentional information filtering and stimulus-orientation. We investigated specificity of relationships between impulsivity and sensitivity to stimulus intensity in bipolar disorder and controls, using intensity–sensitivity of auditory evoked potentials. Seventy-six subjects (37 healthy controls, 39 with bipolar disorder) were administered an intensity–sensitivity paradigm. Additional measures included Barratt Impulsiveness Scale (BIS-11) and Eysenck Impulsivity and Venturesomeness scores. State-dependent rapid-response impulsivity was measured using the Immediate Memory Task. Intensity-sensitivities of the auditory evoked P1N1, N1P2, P1, N1, and P2 potentials were assessed as the slope of amplitude relative to loudness. Analyses used general linear models (GLM) with impulsivity-related measures as dependent variables and age, gender, education, and diagnosis as dependent variables. BIS-11 total, motor, and attentional impulsivity scores correlated positively with pre-attentional N1 and P1N1 intensity–sensitivity slopes in bipolar disorder, but not in controls. BIS-11 nonplanning and Eysenck Venturesomeness scores did not correlate with intensity–sensitivity. Intensity–sensitivity slopes did not correlate with rapid-response impulsivity. Correlations between N1 or P1N1 slopes and BIS-11 scores in bipolar disorder were not affected by age, education, WAIS, treatment, symptoms, or gender. Trait impulsivity in bipolar disorder may be related to poorly modulated stimulus-driven late pre-attentional responses to stimuli, potentially resulting in exaggerated responses to intense stimuli even before conscious awareness. Components of trait impulsivity are physiologically heterogenous relative to intensity–sensitivity.     

The relations among putative biorisk markers in schizotypal adolescents: minor physical anomalies, movement abnormalities, and salivary cortisol.

BACKGROUND: Evidence suggests that prenatal insult may play a role in the etiology of psychotic disorders. Minor physical anomalies (MPA) are an indicator of abnormal fetal development and are elevated in individuals at genetic and behavioral risk for psychosis. Yet, there has been little empirical research on the relationships between MPAs and other neurobiological risk indicators. We hypothesized that the frequency of MPAs (an external marker of prenatal central nervous system [CNS] disruption) would be associated with two other biomarkers suggestive of disruptions in fetal neurodevelopment: movement abnormalities (an indicator of striatal abnormalities) and heightened cortisol secretion (an indicator of hypothalamic-pituitary-adrenal [HPA]/hippocampal function). METHODS: Participants with schizotypal personality disorder (SPD; n = 39) and both normal (n = 47) and other personality disorders (n = 28) control subjects were administered structured diagnostic interviews and assessed for MPAs, movement abnormalities, and salivary cortisol. RESULTS: Schizotypal personality disorder participants showed significantly greater MPAs and movement abnormalities and higher cortisol than both the normal and other personality disorders groups. Hierarchical linear regression analyses revealed that higher rates of MPAs were linked with greater movement abnormalities and salivary cortisol. CONCLUSIONS: The findings suggest that MPAs serve as a marker of neurodevelopmental abnormalities that affect striatal and hippocampal regions.