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

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.

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

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.

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.

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.

Comparative dermatoglyphic study of schizophrenic patients: evidence of the neurodevelopmental model of schizophrenia.

AIM: The aim of the present study was to establish the discriminating value of dermatoglyphic traits between schizophrenic patients and mentally healthy individuals. PATIENTS AND METHODS: The study included 76 schizophrenic inpatients (43 men, 33 women, mean age 31.47 years), who satisfied the DSM-IV criteria for a diagnosis of schizophrenia and 82 mentally healthy subjects of Bulgarian origin of mean age 39.24 years. Fingerprints were obtained by the ink method. Ridge count was read by the method of Cummins and Midlo. RESULTS: The male schizophrenic patients showed a significantly higher total finger ridge count of each hand and TFRC than the control group. On the right hand, statistically significant differences were found for D2 and D5. On the left hand, the differences reached statistical significance for L1, L2 and L5. The schizophrenic females had lower ridge count than the control group females. The differences were most expressed for the total ridge count of the left hand (TFRCL) and total ridge count of both hands (TFRC), but did not reach statistical significance. On the right hand the greatest between-group differences were found for D1 and D4, which were just short of reaching statistical significance (p > 0.05). On the left hand the greatest differences (almost reaching statistical significance) were found for L1. Of the other fingers the greatest differences showed L3 and L4. CONCLUSION: Total finger ridge count appears to be a sensitive trait indicating disorders of prenatal neurodevelopment in schizophrenia.

Computertomographic findings of structural brain anomalies in schizophrenic patients in support of the neurodevelopmental hypothesis of the disorder.

AIM: The aim of the study was to make a comparative CT examination of schizophrenic patients and find lifetime criteria for recognition of brain changes in schizophrenia. MATERIAL AND METHODS: Twenty-two schizophrenic inpatients (mean age 32.86 +/- 2.65 yrs) satisfying the DSM-IV criteria for schizophrenia were examined. The control group comprised 27 clinically healthy subjects (16 men, 11 women, mean age 46.44 +/- 2.32 yrs) all of Bulgarian ancestry. All subjects underwent CT examination without venous enhancement at an examination angle of + 15 degrees-20 degrees in relation to the orbitomeatal line. Cortical atrophy was assessed according to criteria determining the external and internal liquor spaces (after Meese and Groome). RESULTS: There is a consistent low-grade enlargement of the brain ventricles. The variables have increased values (decreased for CMI) in the schizophrenic patients compared with the controls. The patients show moderately increased width of the lateral sulcus and brain convexity sulci. CONCLUSION: The brain tissue loss and enlarged extracerebral space suggest that the observed evidence of cortical loss in schizophrenic patients reflects a pathological process operating before completion of the brain growth.

Fluctuating asymmetry in dermatoglyphic traits in schizophrenic patients.

AIM: The aim of the present study was to establish the validity of fluctuating asymmetry in dermatoglyphic traits as a sign of prenatal injury of schizophrenic patients. MATERIAL AND METHODS. The subjects for this study were 76 schizophrenic inpatients (43 men, 33 women, mean age 31.47 yrs) who satisfied DSM-IV criteria for a diagnosis of schizophrenia and 82 mentally healthy subjects of Bulgarian origin (mean age 39.24 yrs). Fingerprint variables obtained by the ink technique were examined. The fingerprints were read using the method of Cummins and Midlo. RESULTS: The schizophrenics tended to show higher degree of discordance in the fingerprint patterns and ridge counts on homologous fingers than the control subjects. There were evident sex-related differences between the schizophrenic patients and the control group of subjects. CONCLUSION: Fluctuating asymmetry appears a promising method for study of schizophrenia, which could contribute to the establishment of connection between prenatal exogenous influences and structural brain alterations.

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.

Minor physical anomalies in schizophrenic patients and normal controls.

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.

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 mentally healthy subjects: Internal consistency of the Waldrop Physical Anomaly Scale.

The aim of the study was to investigate the prevalence of minor physical anomalies in mentally healthy subjects by using the Waldrop Physical Anomaly Scale and to assess the reliability (internal consistency) of the scale. The subjects were 82 mentally healthy individuals (42 men, 40 women) of Bulgarian origin who were examined for minor physical anomalies. Mentally healthy individuals show a low mean score of minor physical anomalies. The anomalies prevail in the craniofacial region. The correlations between the anomalies are low, which implies poor internal consistency of the scale, probably due to the heterogeneity of the anomalies in terms of location, character, and time of prenatal development and adversity. Providing a base for comparative studies of developmental disorders, the findings infer the necessity of a more reliable scale for examination of informative morphogenetic variants which can distinguish between minor malformations and phenogenetic variants and suggest the period of prenatal adversity.