Stefan T. Sivkov

Minor physical anomalies in schizophrenic patients and normal controls.

Abstract The Aim of the study is to investigate the rate and topographical pattern of minor physical anomalies in schizophrenic patients and normal subjects and determine their value in predicting the patient-control status. Seventy-six schizophrenic inpatients (43 men, 33 women) and 82 normal control subjects (42 men, 40 women) were examined for minor physical anomalies on the Waldrop scale. Schizophrenics showed a higher rate for almost all examined anomalies, the differences reaching statistical significance for six of them: fine electric hair, epicanthus, high/steepled palate, tongue with smooth/rough spots, third toe the second, and big gap between I and II toes. They have significantly higher values for 5 out of 6 body regions and for the total anomalies score. Anomalies in schizophrenics show higher prevalence in the craniofacial complex than the periphery, but the periphery is also considerably stigmatized. Seven anomalies distinguish patients from controls, classifying correctly 81.6% of the patients and 82.9% of the controls. Some anomalies show an almost equal rate in the schizophrenics and the controls, while the rate of others is more than 10 times greater in the patients (odds ratios range: 1.0 to 10.9). Viewed within the multifactorial-polygenic threshold model of liability to a disease, minor physical anomalies might reflect a type of neurodevelopmental risk factor, which by interaction with other genetic or environmental factors could result in passing a threshold and producing symptoms of the disorder, at least in one subpopulation of schizophrenics.

Internal consistency of Waldrop Physical Anomaly Scale in schizophrenic patients

The aim of the study is to investigate the reliability (internal consistency) of the Waldrop Physical Anomaly Scale in patients with schizophrenia. The subjects were 76 schizophrenic patients (43 men, 33 women) and 82 normal controls (42 men, 40 women) of Bulgarian origin who were examined for minor physical anomalies. The correlations between the anomalies are low in schizophrenia, which indicates poor internal consistency of the scale, probably due to the heterogeneity of the anomalies in terms of location, character, and time of prenatal development. Some sex-related differences in the scales reliability are indicated. The findings suggest the necessity of a more comprehensive scale by including informative morphogenetic variants, which can provide reliable anomaly assessment, distinguishing between minor malformations and phenogenetic variants and indicating the possible period of prenatal adversity.

Sexual dimorphism in minor physical anomalies in schizophrenic patients and normal controls

The aim of the current study was to investigate the gender effecton minor physical anomalies (MPA) in schizophrenic patients and normal controls. Seventy-six schizophrenic patients (43 males and 33 females) and 82 normal control subjects (42 males and 40 females) were examined for MPA using a modified version of the Waldrop Physical Anomaly Scale. Men tended to be more stigmatized with MPA than women both in normal subjects and in schizophrenics (with this difference slightly expanding in schizophrenics). In both genders schizophrenic patients were significantly more likely to have MPA than normal controls, but the difference tended to be more pronounced in males. There was a tendency towards sex-related predilection for the increase of MPA in schizophrenics in terms of individual anomalies and topographic regions affected. Among schizophrenics, genders showed a somewhat opposite topography of MPA stigmatization, with relatively more pronounced peripheral dysmorphy in males and craniofacial dysmorphy in females. These data suggest greater vulnerability of the male fetus to endogenous or exogenous factors and different susceptibilities to developmental adversities in male and female schizophrenics. This finding is in accord with the increasing evidence that sex differences in the epidemiology of schizophrenia may be broader and more fundamental than previously thought.

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.

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

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.

Brain-derived neurotrophic factor and its serum levels in schizophrenic patients.

ABSTRACT INTRODUCTION: Neurotrophins have an important role in regulating the development and maintenance of the peripheral and central nervous systems’ function. Thus, the neurotrophin hypothesis of schizophrenia has postulated that the changes in the brain of schizophrenic patients are the result of disturbances of developing processes involving these molecules. AIM: We analyse in the present study the changes in the serum levels of brain-derived neurotrophic factor (BDNF) in schizophrenic patients as possible epiphenomena of underlying alterations of the neurotrophic factor in central nervous system, reflecting its role in the pathophysiology of schizophrenia. PATIENTS AND METHODS: Twenty-one schizophrenic patients satisfying the DSM-IV criteria for diagnosis of schizophrenia were enrolled in the study. The control group consisted of 28 age-matched mentally healthy subjects. Serum BDNF levels were determined in patients and normal controls using ELISA (Chemicon International, USA & Canada). The data were analyzed statistically with Student’s t- test in SPSS 9.0. RESULTS: The serum BDNF levels were lower in the schizophrenic patients than in the control subjects, reaching statistically significant difference (t = 2.72, p = 0.009). Female patients had lower serum BDNF levels than the male patients but the difference fell short of statistical significance (t = 0.1, p = 0.9). CONCLUSIONS: The BDNF reduction in serum indicates a potential deficit in neurotrophic factor release in patients with schizophrenia and support the concept that BDNF might be associated with schizophrenia РЕЗЮМЕ ВВЕДЕНИЕ: Нейротрофины играют важную роль в процессе развития и в поддержке функций периферической и центральной нервной систем. Согласно нейротрофической гипотезе шизофрении изменения в мозгу пациентов с шизофренией являются результатом нарушений в процессе развития, в которые включены эти молекулы. ЦЕЛЬ: В настоящем исследовании авторы анализируют изменения в сывороточных уровнях BDNF у пациентов с шизофренией как вероятный эпифеномен предыдущих нарушений этого нейротрофического фактора в ЦНС, отражающие его роль в патофизиологии заболевания. ПАЦИЕНТЫ И МЕТОДЫ: 21 пациента (покрыты DSM-IV критерии диагноза „шизофрения”) включено в настоящее исследование. Контрольная группа состоит из 28 психически здоровых индивидов. Пациенты и здоровые индивиды одного и того же возраста. Сывороточные уровни BDNF определены иммунометрически с помощью ELISA анализа. Полученные данные анализированы Student’s t- test-ом в SPSS 9.0. РЕЗУЛЬТАТЫ: Сывороточные уровни BDNF у больных шизофренией более низкие по сравнению с уровнями у здоровых индивидов, достигая статистически значимой разницы (t = 2.72, p = 0.009). Пациенты женского пола показывают более низкие уровни BDNF по сравнению с мужчинами, но разница не достигает статистической значимости (t = 0.1, p = 0.9). ЗАКЛЮЧЕНИЕ: Редукция в сывороточных уровнях BDNF предполагает возможный дефицит в продукции этого нейротрофического фактора и подкрепляет идею, что BDNF можно связать с шизофренией

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

ABSTRACT 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 РЕЗЮМЕ ВВЕДЕНИЕ: Образование и детерминирование индивидуального дерматоглифического рисунка представляет собой сложный процесс, волнующий исследователей еще со времени возникновения дерматоглифики как наука. Ранняя дифференциация папиллярных отпечатков, (признак индивидуальности) и сравнительно нетрудные методы получения и сохранения отпечатков, дают возможность надежно исследовать дерматоглифы, а также и поставить себе целью найти их связь с определенными характеристиками при ряде заболеваний, в том числе и при психических расстройствах. ЦЕЛЬ: Настоящий обзор знакомит с литературными данными ряда клинических и теоретических исследваний дерматоглифических признаков преимущественно при шизофрении, подкрепляя нейроонтогенетическую гипотезу развития психических заболяваний. После анализирования теорий формирования папиллярных рисунков и сложных взаимоотношений между папиллярными изображениями и центральной нервной системой во время ранних периодов их эмбрионального развития сделан опыт представить дерматоглифы как возможный биологический маркер нарушенного развития. ЗАКЛЮЧЕНИЕ: Наличие противоречий в дермотоглифической характеристике при психических расстройствах, о которых свидетельствуют многие литературные данные, указывает на необходимость в дополнительных исследованиях этих биологических маркеров с целью установить их место в нейроонтогенетической модели возникновения этих заболеваний

Neurotrophic Factor Receptors trkB and trkC in Experimental Model of Lesion in Rat Brain Structures in Schizophrenia.

Abstract INTRODUCTION: The maldevelopmental model of schizophrenia postulates pathological alterations in embryonal neurogenesis as the etiopathogenetic basis of schizophrenic psychoses. The neurotrophic factor hypothesis explains these neuropathological abnormalities as the result of alterations of the neurotrophin system caused by different mechanisms such as a genetic, infectious and traumatic factors. The tyrosine-kinase containing receptors trkB and trkC mediate growth-promoting effects of neurotrophins and respond to changes in neurotrophic factors availability. AIM: The aim of the present study was to establish the expression pattern of trkB and trkC in rat brain structures by a developmental model of schizophrenia. MATERIALS AND METHODS: On cryostat coronal brain sections of control and lesioned rats (after infusion of ibotenic acid solution bilaterally into the hippocampal formation), immunoreactions for trkB and trkC were performed. RESULTS: We found diminished expression of trkB and trkC in the hippocampal formation of lesioned animals compared to the controls. Quantitative measurements of immunohistochemical reactions intensity and statistical analysis confi rmed the reduced immunoreactivity for antigens under study (trkB and trkC) in the positive hippocampal neurons of 56-day-old lesioned rats compared to the control animals. CONCLUSION: The observed downregulation of neurotrophic factor receptors expression may compromise the function and plasticity of hippocampal formation in schizophrenic brains. Резюме ВВЕДЕНИЕ: Модель шизофрении, связанной с нарушениями в развитии постулирует патологические отклонения в эмбриональном нейрогенезе в качестве этиопатогенетической основы шизофренических психозов. Гипотеза о нейротрофических факторах объясняет данные нейропатологические отклонения как результат нарушений в системе нейротрофинов, вызванных различными генетическими, инфекциозными и травматическими факторами. Тирозинкиназные рецепторы trkB и trkC опосредуют эффекты нейротрофинов, стимулирующих рост и соответствуют изменениям в их наличности. ЦЕЛЬ: Целью настоящего исследования является установление модели экспрессии trkB и trkC в мозговых структурах крысы при экспериментальной модели шизофрении. МАТЕРИАЛЫ И МЕТОДЫ: На криостатных срезах мозга контрольных и испытуемых крыс (после билатеральной инфузии изибутановой кислоты в гиппокампальную формацию) была прослежена иммунореактивность на trkB и trkC. РЕЗУЛЬТАТЫ: Наш анализ выявил заниженную экспрессию рецепторов trkB и trkC в гиппокампальной формации испытуемых животных по сравнению с контрольными. Количественное измерение интенсивности иммуногистохимических реакций и статистический анализ подтвердили понижение иммунореактивности исследуемых антигенов (trkB и trkC) в позитивных гиппокампальных нейронах у испытуемых крыс 56-дневного возраста по сравнению с иммунореактивностью контрольных животных. ЗАКЛЮЧЕНИЕ: Установленное понижение в экспрессии рецепторов нейротрофических факторов можно рассматривать в связи с нарушением функции и пластичности гиппокампальной формации в мозге при шизофрении.