Effective Connectivity Between the Orbitofrontal Cortex and the Precuneus Differentiates Major Psychiatric Disorders: Results from a Transdiagnostic Spectral DCM Study.

BACKGROUND & OBJECTIVE: We have previously identified aberrant connectivity of the left precuneus, ventrolateral prefrontal cortex, anterior cingulate cortex, and anterior insula in patients with either a paranoid (schizophrenia), or a depressive syndrome (both unipolar and bipolar). In the current study, we attempted to replicate and expand these findings by including a healthy control sample and separating the patients in a depressive episode into two groups: unipolar and bipolar depression. We hypothesized that the connections between those major nodes of the resting state networks would demonstrate different patterns in the three patient groups compared to the healthy subjects. METHODS: Resting-state functional MRI was performed on a sample of 101 participants, of which 26 patients with schizophrenia (current psychotic episodes), 24 subjects with Bipolar Disorder (BD), 33 with Major Depressive Disorder (MDD) (both BD and MDD patients were in a current depressive episode), and 21 healthy controls. Spectral Dynamic Causal Modeling was used to calculate the coupling values between eight regions of interest, including the anterior precuneus (PRC), anterior hippocampus, anterior insula, angular gyrus, lateral Orbitofrontal Cortex (OFC), middle frontal gyrus, planum temporale, and anterior thalamus. RESULTS & CONCLUSION: We identified disturbed effective connectivity from the left lateral orbitofrontal cortex to the left anterior precuneus that differed significantly between unipolar depression, where the influence was inhibitory, and bipolar depression, where the effect was excitatory. A logistic regression analysis correctly classified 75% of patients with unipolar and bipolar depression based solely on the coupling values of this connection. In addition, patients with schizophrenia demonstrated negative effective connectivity from the anterior PRC to the lateral OFC, which distinguished them from healthy controls and patients with major depression. Future studies with unmedicated patients will be needed to establish the replicability of our findings.

Dermatoglyphics--a possible biomarker in the neurodevelopmental model for the origin of mental disorders.

INTRODUCTION: Dermatoglyphic pattern formation and differentiation are complex processes which have been in the focus of research interest ever since dermatoglyphics became a science. The patterns' early differentiation and genetic uniqueness as well as the relatively simple methods used to obtain and store fingerprints make it possible to study the relationship between certain dermatoglyphic characteristics and the underlying pathological processes in a number of diseases, including mental disorders. AIM: The present review reports published data from fundamental and clinical studies on dermatoglyphics primarily in schizophrenia and bipolar disorder to lend additional support for the neurodevelopmental hypothesis in the etiology of these disorders. Following an analysis of the theories of dermatoglyphics formation and the complex association between ridge patterns and central nervous system in early embryogenesis, an attempt is made to present dermatoglyphics as possible biological markers of impaired neurodevelopment. CONCLUSIONS: The contradictory data in the literature on dermatoglyphics in mental disorders suggest the need for further studies on these biological markers in order to identify their place in the neurodevelopmental etiological model of these diseases.

Minor physical anomalies in schizophrenia and bipolar I disorder and the neurodevelopmental continuum of psychosis.

OBJECTIVES: Minor physical anomalies (MPAs) have been investigated by numerous studies in patients with schizophrenia in support of the neurodevelopmental hypothesis of the disorder, but have rarely been examined in patients with bipolar disorder or in direct comparisons between the two conditions. The main objective of the present study was to compare the prevalence of MPAs in psychiatrically healthy controls, patients with bipolar I disorder, and patients with schizophrenia. METHODS: A slightly modified version of the Waldrop Physical Anomaly Scale was used to assess MPAs in psychiatrically healthy controls (n = 103), patients with bipolar I disorder (n = 61), and patients with schizophrenia (n = 128). RESULTS: In five out of six topographic regions (mouth, feet, head, eyes, and ears) there was a pattern of lowest regional MPA scores in controls, intermediate in bipolar I disorder, and highest in schizophrenia. The cephalofacial composite score and the total MPA score showed the same pattern, with all between-group differences being statistically significant. Seven individual MPAs in the discriminant analysis model contributed independently to the prediction of the triple-dependent status of 'psychiatrically healthy control, bipolar I disorder patient, schizophrenia patient': high/arched palate, fine electric hair, large gap between first and second toes, third toe ≥ second toe, epicanthus, malformed ears, and furrowed tongue. CONCLUSIONS: Our findings support the existence of a continuum of neurodevelopmental adversity within the clinical spectrum of psychosis, with bipolar I disorder occupying an intermediate position between psychiatric health and schizophrenia.

Discriminating value of total minor physical anomaly score on the Waldrop scale between patients with bipolar I disorder and normal controls.

Minor physical anomalies (MPAs) are slight structural aberrations indicative of abnormal neurodevelopment. Most studies of MPAs in bipolar disorder have yielded limited results. We attempted to assess the potential value of MPAs as a classifying test in the status bipolar I patients vs. normal controls. Sixty one bipolar I patients and 103 controls were evaluated for MPAs using a slightly modified version of the Waldrop scale. The specificity, sensitivity and predictive value of different total MPA (MPA-T) scores were determined. The cut-off MPA-T scores that optimally discriminated patients from controls (exhibiting the most balanced sets of sensitivity, specificity, positive and negative predictive values) were MPA-T ≥ 4 and MPA-T ≥ 5. These values set a "border zone" in which bipolar I patients began to prevail significantly over controls. The latter presented most frequently with MPA-T ≤ 3 and rarely with MPA-T ≥ 6. Bipolar I patients prevailed among outliers (subjects with significantly higher MPA-T scores). Our data establish MPA-T score as a reliable index in distinguishing between bipolar I patients and normal controls and are consistent with the hypothesis of abnormal neurodevelopment in bipolar disorder.

Minor physical anomalies in patients with bipolar I disorder and normal controls.

BACKGROUND: The neurodevelopmental hypothesis is well established in schizophrenia but has received modest empirical support in bipolar disorder. In schizophrenia it is partly based on the higher prevalence of minor physical anomalies (MPAs), established by many well controlled studies. No studies with comparable designs have been performed in bipolar disorder. The present study aims to establish the rate and topographic distribution of MPAs in bipolar I patients. METHODS: The subjects were 61 patients (25 men, 36 women) with bipolar I disorder and 103 normal subjects (49 men, 54 women) who were examined for MPAs using a modified version of the Waldrop Physical Anomaly Scale. RESULTS: The bipolar I patients showed significantly higher regional MPA scores in 3 distinct regions - mouth, feet and head, as well as in the overall scores for the craniofacial complex, the periphery and the total MPA score. Differences were statistically significant for 3 anomalies - high/steepled palate, big gap between I and II toes and furrowed tongue that made significant contribution to the prediction of the patient-control status in a discriminant analysis model. CONCLUSIONS: Our data suggest that aberrant processes of neurodevelopment may contribute to the etiology of bipolar I disorder. The field is open for further research using modern instruments and designs in order to identify potential biological markers for bipolar disorder.

Biomarker profile of minor physical anomalies in schizophrenia patients.

AIM: The aim of this study was to determine the frequency and topographical distribution of minor physical anomalies (MPAs) in schizophrenia patients and control subjects, and the ability of the items of the Waldrop scale to predict the patient-control status. MATERIAL AND METHODS: 128 schizophrenic patients (66 men, 62 women) and 103 normal controls (49 men, 54 women) were evaluated for MPAs with a modified version of the Waldrop scale. RESULTS: Compared with controls, schizophrenia patients showed a higher incidence of almost all studied MPAs, differences being statistically significant for 12 items: fine electric hair, abnormal hair whorls, epicanthus, adherent ear-lobes, lower edges of the ears extending backward/upward, malformed ears, asymmetrical ears, high/arched palate, furrowed tongue, smooth/rough spots on the tongue, III toe > or = II toe, big gap between I and II toe. Some anomalies occurred with almost equal frequency in schizophrenic patients and controls, while others were more than 10 times more common in patients (odds ratio: 0.62 - 10.55). The distribution frequency of MPAs in schizophrenia tended to increase in the cranial direction. Nine predictor MPA biomarkers successfully distinguished 81.10% of patients, 81.55% of controls, and 81.30% of all examined subjects. CONCLUSIONS: The elevated incidence of MPA biomarkers in schizophrenia patients implies impaired neurodevelopment that increases the risk for the development of schizophrenia. The pattern of changes in the morphological characteristics suggests they may be a random outcome of a general neurodevelopmental defect or may reflect different neurodevelopmental defects that allow better characterization of schizophrenia patients subgroups.