Juvenile Schizophrenia Research Articles

Pilot Study to Detect the Repertoires of T-Cell Receptor Gamma Chains in Patients with Juvenile Schizophrenia

Disfunction of immune system and neuroinflammation may play a role in pathogenesis of schizophrenia. The role of adaptive immune system has to be elucidated. We present a pilot study to test the methodology of profiling of immune repertoires of the TCR gamma chain by deep sequencing using several patients with juvenile schizophrenia and unaffected control subjects. The clonotype profiles were revealed and their diversity and presumable differences in structure of CDR3 TRG region of functional clones in juvenile schizophrenia and controls were estimated. This approach is perspective for further comprehensive study of changes in adaptive immune system in representative cohorts of patients with different forms of schizophrenia.

Pilot Study to Detect the Repertoires of T-Cell Receptor Gamma Chains in Patients with Juvenile Schizophrenia

Pilot Study to Detect the Repertoires of T-Cell Receptor Gamma Chains in Patients with Juvenile Schizophrenia

Dysfunction of microstructure and metabolism in corpus callosum in juvenile schizophrenia

IntroductionThe corpus callosum (CC) is one of the important structures responsible for communication between the brain hemispheres. Its role is particularly important in cognitive tasks performance, information processing, concentration of attention, in mnestic processes. The corresponding dysfunctions are the major symptoms of schizophrenia, and hence, structural characteristics of CC in schizophrenics are in the focus of attention.ObjectivesThe aim of the study was to analyze the microstructural and metabolic features of the corpus callosum in recently onset schizophrenia.MethodsThe study was carried out in 13 men with juvenile endogenous paroxysmal psychosis (disease standing ≤ 5 years after first manifestation) aged 17-27 years (median 22.0±3.1 years). The studies were carried out during unfolding remission or in remission. Control group consisted of 15 mentally healthy young men (18-28 years). MRI and 1H-MRS studies were carried out on Achieva 3T MRI scanner device (Phillips). Diffuse tensor images were obtained in the axial plane using echo-planar pulse sequence. Diffuse gradients were applied in 32 noncolinear vectors. The spectra were recorded by single voxel 1H-MRS. The spectroscopic voxel (2×1×1 cm) was placed in the CC genu region. The PRESS sequence was used (TR/TE=1500/40 msec).ResultsStatistical analysis showed no abnormal diffusion values in the CC splenium in the patients. Significant changes in the parameters were found in the CC genu. The values of ADC and RD increased, while FA coefficient decreased in the CC genu of patients with the initial stage of schizophrenia; PD values were normal. The increase of RD in the presence of unchanged PD indicated a decrease of water diffusion velocity and anisotropy in the direction perpendicular to the axon orientation. A typical 1H-MRS of the CC genu was presented in Figure 1. The results of statistical analysis of metabolite signal intensities in the CC genu of patients and normal subjects were presented in Figure 2. NAA level was reduced significantly in the patients. No appreciable changes in Cho values in the CC genu were detected in the patients vs. normal subjects.Image:Image 2:ConclusionsThe increase of RD could be caused by several factors: impairment of myelin membranes, axon damage because of impairment of axon cytoskeleton, and changed organization of fibrils. Our results showed that RD increase in patients with early schizophrenia did not conform to active demyelination, which was proven by the normal level of Cho, while axon damage, shown by low level of NAA, did not lead to PD reduction.The decrease of NAA level detected in our study indicated axonal damage in the CC genu of patients in the early stage of schizophrenia. The increase of RD in the presence of normal Cho level seemed to indicate disorders in the axon cytoskeleton damage, but not active demyelination.Disclosure of InterestNone Declared

A 45-year follow-up study of adolescent schizophrenia. Part IV: Clinical status and level of social adaptation 5 years after the first hospitalization in the context of illness course and long-term social functioning of patients.

Research on predictors of adolescent schizophrenia, especially those based on long-term follow-up studies, is rare in the literature. In our analysis, we examine the relationship of the clinical status and level of social adaptation 5 years after the first hospitalization with clinical and social indicators of the illness course. 69 patients at the average age of 16 years (time point 0), hospitalized due to schizophrenia (retrospectively re-diagnosed according to ICD-10 criteria) and re-examined 5 years later (time point 1 - personal examination of 41 individuals), were re-evaluated for clinical and social parameters 45 years after their initial hospitalization (time point 2 - personal examination of 21 individuals). In addition to the personal survey, other methods of data collection were used, including hospital queries. The clinical picture of schizophrenia 5 years after the first hospitalization described by the severity of psychopathology, as well as other parameters of the clinical status (e.g., insight, clinical improvement, relational abilities, GAF), revealed numerous and various correlations both with the symptomatic picture and clinical course of schizophrenia 45 years after the first hospitalization as well as with distant social functioning of the subjects. In the analyses, high prognostic significance was also revealed by the level of psychotic relapse, the presence of auto-aggressive tendencies, and the quality of school and professional adaptation assessed at time point 1. he level of functioning achieved by the patient in clinical and social areas during the first 5 years after their initial hospitalization proved to be an important prognostic factor in adolescent schizophrenia.

A 45-year follow-up study of adolescent schizophrenia. Part I: Premorbid values of psychological and relational indicators in the context of illness course and long-term social functioning of patients.

Research on predictors of adolescent schizophrenia, especially those based on long-term follow-up studies, is rare in the literature. In our analysis, we examine the relationship between the premorbid functioning of the respondents and clinical and social indicators of the illness course. 69 patients at the average age of 16 years (time point 0), hospitalized due to schizophrenia (retrospectively re-diagnosed according to ICD-10 criteria) and re-examined 5 years later (time point 1 - personal examination of 41 individuals), were re-evaluated for clinical and social parameters 45 yearsafter their initial hospitalization (time point 2 -personal examination of 21 individuals). Premorbid indicators of mood, life drive, emotional expression, level of social withdrawal, intelligence, anxiety, development of sexual and aggressive drive, and family and extra-family relational life revealed numerous and various correlations with both the symptomatic picture and clinical course of schizophrenia as well as distant social functioning of the subjects. Variables of the greatest prognostic value were: the emotional attitude of "moving away from" people and the world, and rich relational life outside the family of origin. These variables revealed opposite correlations, especially with the severity of negative symptoms, the level of late insight and regression, the quality of professional life and GAF scores, with the correlations of rich relational lifeto be assessed as positive and the correlations of attitude of "moving away from" as negative. The harmonious development of drive as well as high intelligence also proved to be significant. The correlations of both of these variables have proved beneficial both in clinical and social terms. The so-called premorbid personality described by several indicators turns out to be an important prognostic factor in juvenile schizophrenia.

The role of inflammation in pathogenesis of juvenile schizophrenia

IntroductionInflammation is now known to be a key factor in the development of schizophrenia. In this regard, the study of the pathogenic role of inflammation in the early stages of schizophrenic process is of particular importance, making it possible to assess its activity and to predict the development of the disease.ObjectivesTo compare the dynamics of inflammatory markers in blood of first-episode psychosis (FEP) patients and people at risk signs for schizophrenia in the course of the treatment. Juvenile depression (JD) with attenuated symptoms of schizophrenic spectrum (ASSS) was investigated as a risk group.MethodsThe patients aged 17-25 years (20 people, of which 10 FEP patients (F20) and 10 JD with ASSS ones (F32.1-2, F32.38, F32.8)) were examined at admission to the hospital and at discharge. The controls consisted of 10 healthy volunteers. Symptom severity was collected using PANSS, SOPS, SANS, HDRS. The inflammation markers (TNF-α, IL-6, IL-10, leukocyte elastase (LE), CRP, α1-proteinase inhibitor (α1-PI), anti-S100-beta antibodies) were determined in blood.ResultsAn increase of inflammatory markers in both groups compared to controls was found (p<0,05). The highest values of IL-6, LE, CRP, α1-PI and anti-S100-beta antibodies in FEP patients were revealed (p=0,03). After the treatment, the positive trend of inflammatory markers in FEP patients (p<0,05), but not in JD with ASSS patients was detected (except LE activity, p<0,05).ConclusionsThe results confirm the pathogenic role of inflammation in the development of endogenous mental disorders. The inflammatory markers studied reflect the activity of the pathological process in the early stages of schizophrenia.DisclosureNo significant relationships.

Neurophysiological Characteristics of Patients with Juvenile Schizophrenia at the Late Follow-Up Stage

Objective. To determine the neurophysiological features of schizophrenia at late (more than 20 years) follow- up and identify correlations between neurophysiological indicators and the clinical characteristics of the disease. Materials and methods. Patients of three groups were studied: those with a predominance of personality changes (group 1, 17 patients), those with negative disorders (group 2, 23 patients), and those with marked positive and negative disorders (group 3, 40 patients). The main study methods were psychopathological and neurophysiological, with assessment of event-linked potentials. Results and conclusions. A statistically significantly greater θ-rhythm frequency and a significantly lower α-rhythm frequency were found in group 3, the dominant frequency of the θ rhythm showing a correlation (positive) with the total score for positive disorders on the PANSS. No statistically significant between-group differences were seen in measures of the P300 wave of auditory event-related potential recorded in the oddball paradigm. These results are considered in the framework of views of the role of θ activity as a marker for hippocampal-prefrontal interactions.

Neurophysiological characteristics of juvenile schizophrenia patients examined at the very remote follow up stage

To determine neurophysiological characteristics of patients with long-term follow up (>20 years) and to find correlations between neurophysiological parameters and clinical features of schizophrenia. The patients were divided into three groups: with predomination of personality changes (group 1, n=17), with negative disorders (group 2, n=23) and with positive and negative disorders (group 3, n=40). A psychopathological method and electroencephalography with evoked potentials testing were used. In group 3, the statistically significant higher frequencies of theta-rhythm and lower of alpha-rhythm were found. Also, theta frequency correlated with PANSS positive scores. The significant intergroup differences by auditory oddball P300 were lacked. The findings are discussed in view of the hypothesis of theta-rhythm as a marker of hippocampal-prefrontal connectivity.

Microstructural and metabolic disorders in CC of juvenile schizophrenia patients

IntroductionThe aim of the study was to analyze the microstructural and metabolic features of the corpus callosum in recently onset schizophrenia.Objectives13 young (17–28 years old) male patients with recently onset schizophrenia (F20, ICD-10) and 15 sex and age matched mentally healthy subjects were examined.Methods3 T Philips Achieva scanner with 8-channel SENSE coil was used. DTI was conducted with EPI SENSE (TR = 9431 ms; TE = 70 ms). The values of diffusion coefficient (ADC), fractional anisotropy (FA), radial (RD) and parallel (PD) diffusivity were calculated using workstation Philips EBWS 2.6.3.4. Spectroscopic voxel (2 × 1 × 1 cm) was placed consequently in the corpus callosum genu and splenium. PRESS (TR/TE = 1500/40) was used.ResultsIn patients, increased ADC (P = 0.02) and RD (P = 0.008), decreased FA (P = 0.008) and NAA (P = 0.03) were found in the corpus callosum genu, No intergroup differences by PD, Cho, Cr, Glx were found in this area. Also, no statistically significant intergroup differences were observed for the DTI and MRS characteristics of the corpus callosum splenium.ConclusionsIt has been shown that RD increase is associated with demyelination process. So, an increase of RD in the present study could reflect demyelination in CC genu. Cells membranes abnormalities should lead to an increase of Cho which was not found. NAA reduction could be caused by reduction of axonal integrity. The latter process is considered to precede demyelination and not to be accompanied by PD rise. Thus, the present study revealed axonal integrity reduction and low demyelination in the genu of the corpus callosum in the early stages of schizophrenia.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Microstructural abnormalities of the corpus callosum and fasciculus uncinatus and auditory information processing in patients with juvenile paroxysmal schizophrenia

One approach to the problem of determining the mechanisms coupling the structure and functions of the brain is studies in clinical populations aimed at assessing the presence or absence of congruence of anatomical/ morphological and functional abnormalities. Magnetic resonance imaging (MRI), including structural MRI and diffusion tensor imaging with tractography, as well as the recording of auditory event-related potentials (ERPs) in the standard two-tone oddball paradigm and the sensory gating paradigm, was conducted in 26 male patients with paroxysmal juvenile schizophrenia and 26 mentally healthy men with no family history of mental illness. MRI abnormalities have been found in the genu of the corpus callosum and fasciculus uncinatus of the left hemisphere of the patients. Reduction of the fractional anisotropy in the genu of the corpus callosum was correlated with P300 reduction in the right temporal region.

Mitochondrial Dysfunction in Schizophrenia: Determination of Mitochondrial Respiratory Activity in a Two-Hit Mouse Model.

Schizophrenia is a chronic mental illness in which mitochondrial dysfunction has been suggested. Our laboratory recently developed a juvenile murine two-hit model (THM) of schizophrenia based on the combination of gestational inflammation, followed by juvenile restraint stress. We previously reported that relevant behaviors and neurochemical disturbances, including oxidative stress, were reversed by the antioxidant lipoic acid (LA), thereby pointing to the central role played by oxidative abnormalities and prompting us to investigate mitochondrial function. Mitochondrial activity was determined with the MitoXpress® commercial kit in two schizophrenia-relevant regions (prefrontal cortex (PFC) and striatum). Measurements were performed in state 3, with substrates for complex I- and complex II-induced respiratory activity (IRA). We observed an increase in complex I IRA in the PFC and striatum in both sexes but an increase in complex II activity only in males. LA treatment prevented this increase only in complex II IRA in males. Expression levels of the different respiratory chain complexes, as well as fission/fusion proteins and protein carbonylation, were unchanged. In conclusion, our juvenile schizophrenia THM shows an increase in mitochondrial activity reversed by LA, specifically in complex II IRA in males. Further investigations are required to determine the mechanisms of these modifications.

Characteristics of the Immune System and the Risk of Developing Endogenous Psychosis at Juvenile Age

Study aim. To investigate immunological parameters at the early stages of development of juvenile schizophrenia. Materials and methods. Immunological profiles were determined in patients aged 16–25 years receiving in-patient treatment. Patients were divided into two groups. Group 1 consisted of 39 patients with psychopathological symptomatology at the non-psychotic level (prodrome group) and group 2 consisted of 38 patients with first onset of endogenous psychosis (psychosis group). Immunological parameters included phagocytic activity, lymphocyte natural killer cytotoxic activity, production of interleukins IL-1, IL-4, IL-10, and interferon γ, and circulating immune complex (CIC) levels. These investigations were performed before and after treatment. Results. The experiments reported here showed that changes in immune system function were seen in patients at the earliest stages of disease development, with activation of proinflammatory and anti-inflammatory interleukins, decreases in phagocytic index and natural killer lymphocyte cytotoxic activity, and phagocytic number. Development of psychosis was associated with persistence of the high level of IL-10 production, the decreased level of natural killer cytotoxic activity, and the decreased phagocytic index, with accumulation of CIC. Conclusions. The authors recommend the use of not only psychotropic, but also immunomodulatory agents at the early stage of the development of endogenous psychosis.

Some Structural-Functional Characteristics of the Dorsolateral Prefrontal Cortex and the Genu of the Corpus Callosum and Auditory Information Processing (P300) in Healthy Subjects and Patients with Juvenile Schizophrenia

The structural-functional characteristics of the dorsolateral prefrontal cortex and genu of the corpus callosum were studied, along with their interaction with electrophysiological markers of selective attention processes in 18 mentally healthy subjects and 22 patients with juvenile schizophrenia at the remission onset stage and in remission. No statistically significant intergroup differences were found in terms of N-acetylaspartate and choline-containing substance levels (assayed by proton magnetic resonance spectroscopy), while fractional anisotropy (measured by diffusion-tensor magnetic resonance tomography) in the genu of the corpus callosum was lower in the patients group. The absence of any statistically significant correlations between neuroimaging characteristics and assessments of the severity of psychopathological disorders, along with occasional correlational interactions with P300 parameters, suggest weak involvement of the study structures in processes determining cognitive impairments in patients with juvenile schizophrenia.

Some Electrophysiological and Hemodynamic Characteristics of the Processes of Auditory Selective Attention in Health and Schizophrenia

Six patients in remission after first episodes of juvenile schizophrenia and seven mentally healthy subjects selected on the basis of age and gender were studied by functional magnetic resonance imaging and recording of evoked potentials, in both cases using the oddball paradigm in the auditory modality. Differences in the parameters of the P300 wave were significant, and significantly greater hemodynamic responses to test stimuli were recorded bilaterally in the supramarginal gyrus and right medial frontal gyrus in patients, pointing to pathology in these areas of the brain in their support for auditory selective attention processes.

Hemodynamic and Biochemical Characteristics of the Prefrontal Cortex after First Episodes of Juvenile Schizophrenia

Authors analyzed biochemical (data obtained by proton MR spectroscopy) and hemodynamic ( data of fMRI) characteristics of the prefrontal cortex in 7 patients with juvenile shift-like schizophrenia examined during remission after the first episode and in 8 mentally healthy subjects matched for sex and age. The between-group differences in the tested parameters were not found, however, the neurobiological features of the prefrontal cortex were correlated with the psychopathological symptoms assessed with the PANSS.

Depressive states at the onset of juvenile schizophrenia

Depressive states at the onset of juvenile schizophrenia

THE INTERPRETATION OF SCHIZOPHRENIC-LIKE BEHAVIOR IN CHILDREN1

It is well known that the recognition of mental abnormality in adults in the early stages is extremely difficult. And it is much more difficult to make a diagnosis of mental disease in children. The criteria of juvenile mental abnormality are ill-defined, and relatively few systematic studies have been made. The problem has been made additionally difficult by the indiscriminate use of the term problem. In general there have been few attempts to construct classifications of juvenile behavior, except in very broad categories. Most workers in the fields of child development and psychiatry have been content to classify behavior into the rather indefinite categories of adjustment and maladjustment. It is obvious that such general classifications are inadequate. They may have a practical value from the standpoint of parent counselling, but exact treatment requires clear-cut differentiation. Greene (2) has shown, for example, that schizophrenic symptoms and the behavior of the mentally defective have been confused in many instances, in part because precise descriptive differentiation was not attempted. Others have noted that many symptoms of mental abnormality are overlooked until the behavior of the child becomes unusually deviant or queer. In this paper the attempt is made to define and describe schizophrenic conditions of children. The data were obtained from examination and observation of seventeen children who were under study for periods of from six months to four years. It is not meant to imply that their symptoms were manifested in the same way as those of adult schizophrenics. The term juvenile schizophrenia is employed in this instance to describe a process of emotional disorganization and personality dissociation, in which serious judgmental defect was the most prominent symptom. The disorientation, the social deterioration and behavior disturbances, with or without hallucinatory, paranoid, or catatonic episodes, were considered to be symptoms of an abnormal process which might well be classified as schizophrenic. It is obvious to anyone with extensive psychiatric experience that it is extremely difficult to define early schizophrenia. The clinical picture of schizophrenia is so variable and the patterns of the various symptoms so indefinite, that most psychiatrists depend to some extent upon a social history in making their diagnoses. It is especially difficult to define a schizophrenic condition in its developmental stages. When an individual shows systematized delusions, hallucinations, paranoid ideas, ideas of reference or catatonic episodes, it is relatively easy to make a diagnosis; but when none of these circumscribed symptoms is present, the diagnosis is often not made until relatively late in the development of the condition, In general, psychiatrists probably agree in defining schizophrenia as a personality disorganization with more or less dissociation and affective disturbances. Whatever abnormal behavior may result from this condition depends at least in part upon the personality, attitudes, interests, and the experiences of the individual and the influence of his environment.