To personalize pharmacotherapy with aripiprazole in patients with schizophrenia via therapeutic drug monitoring (TDM).
TDM of aripiprazole (ARI) and its active metabolite dehydroaripiprazole (DHA) ...was performed for patients diagnosed with schizophrenia (ICD-10 F20.00; F20.01; F20.02). Thirty-six parameters were assessed. To carry out TDM, the method of high-performance liquid chromatography with mass spectrometry was chosen employing a validated method.
TLM was performed in a group of young patients: 26.5±10.1 years old, average weight 77.2±16.2 kg, average PANSS score 81.4±21.4, UKU score 14.5±3.9. An average ARI concentration was 18.4±7.9 mg, serum ARI concentration 417.9±362.4 ng/ml, serum DHA concentration 117.5±116.1 ng/ml and the total concentration 535.4±478.5 ng/ml. Equations of correlation dependences of concentration on dose are obtained for ARI and DHA.
The results show the significant metabolism of ARI. A combined determination of the main substance and its active metabolite DHA in the patient's blood serum is advisable for correct assessment of the TLM result in patients with mental diseases.
We analyzed morphometric MRI parameters indirectly attesting to structural changes in the supragranular layer in 33 non-converted individuals at clinical high risk for endogenous psychosis (follow-up ...period of 6.7±0.6 years) and in 34 sex- and age-matched healthy controls. In the group of clinical high-risk individuals, changes indicative of potential predominance of supragranular thinning in comparison with a decrease of infragranular cortical layer thickness were revealed. The results are discussed in the context of the concepts of resilience and risk markers of developing endogenous psychosis.
Objectives
. To identify the structural features of the gray matter of the cerebral cortex in patients with depression at clinical high risk of psychosis.
Materials and methods
. Nineteen ...right-handed male patients with juvenile depression who met the criteria for a high risk of psychosis, along with 20 sex- and age-matched mentally healthy subjects as a control group, underwent clinical and MRI investigations. T1-weighted images were processed in FreeSurfer 7.1.1 to obtain average cortical gray matter thickness, subcortical volume, and amygdalar nucleus volume for each subject. Between-group comparisons were made and correlations with psychometric measures (SOPS, HDRS) were calculated.
Results
. Lower cortical thickness was found in patients in the left (
p
= 0.002) and right (
p
= 0.003) postcentral gyrus, along with greater thickness in the right posterior cingulate cortex (
p
= 0.003) and the anterior part of the anterior cingulate cortex (
p
= 0.001).
Conclusions
. This picture may reflect changes in the cerebral cortex at the early stages of the endogenous process, including reductions in gray matter in some areas and changes in the opposite direction in others (a relationship between the latter and altered ontogenesis and/or certain compensatory changes cannot be excluded).
The aim of the present study was, within the framework of the concept of “clinical high risk for psychosis,” to identify functional characteristics of the brain (based on resting-state fMRI data) and ...neuropsychological characteristics in 27 patients with non-psychotic mental disorders, with attenuated schizophrenia symptoms which had not converted during a long observation period, as compared with 24 patients with first-episode schizophrenia, and 27 mentally healthy subjects. The main group was characterized by higher levels pf BOLD coherence in the visual cortex of the right hemisphere and higher functional connectivity between the occipital component of the visual network and a salience network component in the right prefrontal cortex (as compared with schizophrenia patients). Both groups of patients showed decreased productivity in verbal fluency tests. The neuroimaging and neuropsychological peculiarities of patients in the main group identified here can be regarded as reflecting an impact of “protective” and “pathological” mechanisms in patients at high risk for schizophrenia.
Objectives.
To compare groups of schizophrenia patients with different levels of functional outcomes and different frequencies of risk variants at polymorphic loci of five candidate genes to create a ...multigene panel and to test its predictive value for long-term disease outcomes.
Materials and methods.
Patients included in this study were divided in terms of the typology used here into three groups with different levels of social functioning. Group 1 patients had the highest levels, while values were significantly lower in group 2 and lowest in group 3. The multigene panel included genes for the type 2A serotonin receptor (5-HTR2a T102C), the serotonin transporter (5-HTTLPR), C-reactive protein (CRP-717A>G), the type 1 angiotensin II receptor (AGTR1 A1166C), and brain-derived neurotrophic factor (BDNF Val66Met). Computation of multigene risk (MGR) was by summation of all the risk alleles carried by a particular patient. For each polymorphism, carriers of the genotype homozygous at the high-risk allele had a value of 2 and heterozygotes had a value of 1; homozygotes at the low-risk allele had a value of 0. MGR Values for a patient could range from 0 to 10 risk alleles.
Results.
Group was found to have a significant effect on MGR (
p
< 0.0001). Between-group differences were also significant (
p
< 0.01). Group 1 contained no carriers of six or more risk alleles and more than 50% were carriers of fewer than five alleles. In group 2, 19.4% of patients were carriers of ≥6 risk alleles, while 31.7% of patients in group 3 carried ≥6 risk alleles. These groups had no carriers of 0–2 risk alleles, while 20.7% of patients group 1 carried 0–2 risk alleles.
Conclusions.
MGR may be a predictor of functional outcome in schizophrenia patients. Low levels of risk alleles (0–4) allowed individuals to be predicted with high probability to have favorable functional outcome in the long-term period of illness.
Objectives.
To identify the clinical and pathopsychological features of juvenile depression with attenuated schizophrenia spectrum symptoms, as well as their value for early differential diagnostic ...and nosological assessment.
Materials and methods.
The study group consisted of 20 patients of juvenile age (19.7 ± 3.7 years) with first depressive episodes with attenuated schizophrenia spectrum symptoms (ASSS) (ICD-10 F32.1, F32.2, F32.3), who were divided into two subgroups: subgroup 1 had attenuated positive symptoms (APS) (19.3%) and subgroup 2 had attenuated negative symptoms (ANS) (45.1%). The comparison group consisted of 11 patients (mean age 19.4 ± 2.9 years) with depression without ASSS (F32.1, F32.2). The psychometric scales HDRS, SOPS, and SANS were used, along with pathopsychological methods and the Adult Personality Traits Questionnaire (APTQ).
Results and conclusions.
There was no significant between-group difference in the severity of depressive disorder. Patients with depression with ASSS, as compared with the comparison group, showed higher total scores on the SOPS (
p
= 0.006) and greater severity of negative disorders on the SANS (
p
= 0.006). Distortion of the generalization process was found in 60.0% of cases, impairments to immediate memory were found in 30.0% of patients, and associations were non-constructive in nature in 10.0% of patients. Indirect data showing that patients of the control group had higher levels of emotional integrity were obtained. These differences suggest that the pathogenesis of depression with ASSS involves not only an afferent mechanism, but also the endogenous schizophrenic process, while ASSS itself may be a reflection of the early stage of schizophrenia or markers for the risk of developing it.
Objective
Clinical and follow-up verification of Attenuated Schizophrenic Symptoms (ASS) in the first youth depressive episode as early markers of the schizophrenic process, establishing further ...variants of the course of the disorder and its outcomes.
Material
s
and
methods.
124 young inpatients (averaged age 19,6±2,3 years) with the first depressive episode with ASS were examined. The control group consisted of 27 patients with youth depression without ASS. All patients have been tracked for at least five years. The average follow-up period was 7,1±1,6 years. The HDRS, SOPS, SANS and PSP scales were used to assess the symptomatic and functional outcomes. Statistical analysis was carried out using STATISTICA 12.
Res
ults.
The typological classification of youth depressions (ASD) with ASS has been developed with the identification of three main types: (1) with attenuated positive symptoms (APS), (2) with attenuated negative symptoms (ANS), and (3) with attenuated symptoms of disorganization. Youth depression with ASS, compared to the control group, is more likely to move into chronic forms, has reliably worse functional and symptomatic outcomes, and is more associated with the diagnosis of schizophrenic spectrum disorders at five years follow-up.
Con
c
lu
s
ion.
Attenuated schizophrenic symptoms in the structure of youth depressions have high affinity to each other, indicating a common pathogenic mechanism of their formation, and also have predicate value as risk factors for schizophrenia.
The article briefly presents an analysis of the development of domestic psychiatry (with an emphasis on research in the field of psychopathology and nosology) from the post-war period (the Great ...Patriotic War) to the era of "perestroika". With the founding of the Institute of Psychiatry of the USSR Academy of Medical Sciences under the leadership of V.A. Gilyarovsky, the study of endogenous diseases was based on a multidisciplinary approach, in which the clinical-psychopathological research method was combined with clinical/biological ones. The most important role of the subsequent school of A.V. Snezhnevsky in describing the syndromes and forms of the course of schizophrenia (G.A. Rotshtein, R.A. Nadzharov, A.B. Smulevich, A.K. Anufriev), its age aspects (E.Ya. Sternberg; M.S. Vrono, G.P. Panteleeva, M.Ya. Tsutsulkovskaya; V.M. Bashina) is reflected. The contribution to psychopathology of other leading Russian psychiatrists, who worked mainly in Moscow and Leningrad research institutions of that period, was noted: students of P.B. Gannushkin - O.V. Kerbikov, V.M. Morozov, D.S. Ozeretskovsky, S.G. Zhislin, as well as G.K. Ushakov, A.E. Lichko, M.M. Kabanov, G.V. Morozov, M.V. Korkina, A.A. Portnov, I.N. Pyatnitskaya and others. The priority of A.V. Snezhnevsky and G.K. Avrutsky with colleagues for the introduction of neuroleptics and other new psychotropic drugs in the treatment of mental illnesses is emphasized. The review ends with the activities of M.E. Vartanyan who headed the country's leading scientific institution in the difficult «perestroika» era and developed the biological approach to mental illness further with the creation of international research programs.
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.
Objective:
To test the general hypothesis that schizophrenia patients have an executive deficit in speech production and the more specific hypothesis that this deficit is more severe when there is a ...greater demand on executive functions.
Materials and methods:
The study included 25 patients with schizophrenia and 27 healthy subjects (control group). All subjects took part in two tests: to tell stories based on a series of pictures and based on a specified theme.
Results and conclusions:
Schizophrenia patients displayed lower measures of programming and shorter texts and phrases than the control group in both tests. Patients’ subject-based stories included grammatical errors, along with the need for leading questions because of difficulties with plot construction; there was also greater dispersion of the length and syntactic complexity of the text. Thus, this study showed that during speech production, schizophrenia patients displayed a deficit of executive functions, which was most marked in the task involving a smaller number of external cues aiding speech planning and production.
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