Emotional disorder assessment system, data creation method, and screening method

Abstract

To provide a novel affective disorder evaluation system that can highly objectively and reliably evaluate affective disorder.SOLUTION: An affective disorder evaluation system includes: an acquisition part for acquiring image data indicating the hippocampus of a subject; and a specification part for specifying volume data indicating a volume of the right hippocampus-amygdala transition part of the subject in accordance with the image data.SELECTED DRAWING: Figure 7

Description

Technical Field

[0001] The present invention relates to an emotional disorder evaluation system, a data creation method, and a screening method.

Background Art

[0002] The present inventor has been conducting research aimed at establishing diagnostic methods and treatment methods for diffuse axonal injury caused by traffic accidents, falls, etc., hypoxic encephalopathy caused by myocardial infarction or stroke, and higher brain dysfunction caused by carbon monoxide poisoning, etc. Without the need for large-scale equipment, a method capable of simply and accurately evaluating the hippocampal function of a subject and an evaluation system for hippocampal function have been proposed (Patent Documents 1-3).

[0003] On the other hand, emotional disorder is a mental disorder having multiple aspects including biological factors, behavioral factors, social factors, and psychological factors, and is characterized by mood changes as the main clinical symptom.

[0004] For example, in Patent Document 1, as a method for determining whether an individual has an emotional disorder or a risk of developing the same, the expression level of connective tissue growth factor (CTGF) in a biological sample derived from the individual is detected, and when the expression level of the CTGF is increased compared to the control expression level of the CTGF, it is described that it is determined that the individual has an emotional disorder or a risk of developing the same.

Prior Art Documents

Patent Documents

[0005]

Patent Document 1

Patent Document 2

Patent Document 3

Patent Document 4

[0006] However, Patent Document 4 only shows an example where CTGF is upregulated in the tonsils of individuals with major depressive disorder (MDD) compared to controls, and its objectivity and reliability are insufficient.

[0007] This invention has been made in view of the above circumstances, and aims to provide a new emotional disorder evaluation system and data creation method that can objectively and reliably evaluate emotional disorders. Furthermore, this invention aims to provide a screening method for compounds that have an effect of improving emotional disorders. [Means for solving the problem]

[0008] To solve the above problems, the emotional disorder evaluation system of the present invention is An acquisition unit that acquires image data representing the subject's hippocampus, A specific unit identifies volume data representing the volume of the right hippocampal-amygdal junction of the subject, based on the aforementioned image data. It is characterized by possessing the following features.

[0009] The data creation method of the present invention is a method for creating data for evaluating the emotional disorder of a subject, The process of obtaining image data representing the subject's hippocampus, The method is characterized by including the step of identifying volume data representing the volume of the right hippocampal-amygdal junction of the subject, based on the aforementioned image data.

[0010] The present invention provides a screening method for compounds having an effect of improving emotional disorders, The method is characterized by including a step of extracting compounds that reduce the volume of the right hippocampal-amygdala junction, using volume data representing the volume of the junction. [Effects of the Invention]

[0011] The emotional disorder evaluation system and data creation method of the present invention allow for objective and highly reliable evaluation of emotional disorders. Furthermore, the screening method of the present invention allows for the extraction of compounds that have an effect of improving emotional disorders. [Brief explanation of the drawing]

[0012] [Figure 1] This is a block diagram illustrating the configuration of an emotional disorder assessment system. [Figure 2] This is a flowchart of the process performed by the emotional disorder assessment system. [Figure 3] This diagram shows an overview of volume determination for the hippocampal subfield. [Figure 4] This figure shows the BOLD signal (Blood Oxygen Level Dependent Signal) in the bilateral hippocampal-amygdal junction (HATA) of a subject with right temporal lobe diffuse astrocytoma. [Figure 5] This figure shows that the volume of the right hippocampal-amygdal junction (right HATA) is increased in subjects with right temporal lobe diffuse astrocytoma. [Figure 6] This figure shows a comparison of hippocampal and amygdala subfield volumes in women with emotional disorders and healthy control groups. It demonstrates that the volume of the right hippocampal-amygdala junction (right HATA) is significantly larger in women with emotional disorders. [Figure 7] This figure shows a comparison of hippocampal and amygdala subfield volumes in women with emotional disorders and healthy control groups. It demonstrates that the volume of the right hippocampal-amygdala junction (right HATA) is significantly larger in women with emotional disorders (P<0.05). [Modes for carrying out the invention]

[0013] The inventor of the present invention has conducted research on the relationship between emotional disorders and the volume of hippocampal subfields, and newly found that an increase in the volume of the right hippocampus-amygdala transition area (hereinafter sometimes referred to as the "right HATA (hippocampus-amygdala-transition area)") is observed in subjects with emotional disorders, and has thus completed the present invention.

[0014] In the present invention, the "emotional disorder" includes, for example, depression, anxiety, bipolar disorder, postpartum depression, mood swings, seasonal emotional disorder, schizoaffective disorder, panic disorder, eating disorder, obsessive-compulsive disorder, and post-traumatic stress disorder (PTSD).

[0015] Hereinafter, an embodiment of the emotional disorder evaluation system and data creation method of the present invention will be described.

[0016] In the present invention, the "evaluation of emotional disorder" includes evaluating the state (presence or absence and degree) of emotional disorder of a subject, or the risk of future onset of emotional disorder, treatment effect, and the like.

[0017] FIG. 1 is a block diagram illustrating the configuration of an emotional disorder evaluation system 100 according to the present embodiment. The emotional disorder evaluation system 100 of the present embodiment is a system for evaluating the emotional disorder of a subject. Specifically, the emotional disorder evaluation system 100 includes a control device 10 and a storage device 20.

[0018] The control device 10 is one or more processors that control each element of the emotional disorder evaluation system 100. Specifically, for example, the control device 10 is constituted by one or more types of processors such as a CPU (Central Processing Unit), SPU (Sound Processing Unit), DSP (Digital Signal Processor), FPGA (Field Programmable Gate Array), or ASIC (Application Specific Integrated Circuit). The control device 10 evaluates the emotional disorder of a subject.

[0019] The storage device 20 is one or more memories that store programs executed by the control device 10 and various data used by the control device 10. The storage device 20 is composed of known recording media such as magnetic recording media or semiconductor recording media, or a combination of multiple types of recording media. Alternatively, a separate storage device 20 (e.g., cloud storage) may be provided, and the control device 10 may perform writing and reading to the storage device 20 via a communication network such as a mobile communication network or the Internet. In other words, the storage device 20 may be omitted from the emotional disorder evaluation system 100.

[0020] As illustrated in Figure 1, the control device 10 of this embodiment implements multiple functions (acquisition unit 11, identification unit 13, and evaluation unit 15) for evaluating the emotional disorder of a subject by executing a program stored in the storage device 20.

[0021] The acquisition unit 11 acquires image data D1 representing the subject's hippocampus and amygdala from the storage device 20. The image data D1 is displayed on a display device (not shown). Image data D1 is, for example, anatomical three-dimensional image data of the hippocampus and amygdala obtained using a known device such as an MRI scanner. When using anatomical three-dimensional image data of the hippocampus, it is preferable to be able to display images for each hippocampal subfield. Specifically, the hippocampal tail, hippocampal peristome, anterior hippocampal peristome, parahippocampal peristome, Ammon's horn (CA)1, CA3, CA4, dentate gyrus granule cell layer (GC-DG), hippocampal molecular layer, hippocampal-amygdal transition region (HATA), and hippocampal fimbria can be displayed. The hippocampal cleft can also be displayed.

[0022] Furthermore, image data D1 may be data that has undergone various image processing, such as motion correction, skull removal, intensity normalization, white matter separation, 3D visualization of gray matter / white matter (tessellation), and brain surface extraction. Such image processing can be performed using, for example, Freesurfer 6.0 (http: / / surfer.nmr.mgh.harvard.edu).

[0023] The identification unit 13 identifies data D2 representing the volume of the subject's right hippocampal-amygdal junction (right HATA) (hereinafter referred to as "volume data"). In this embodiment, the identification unit 13 identifies the volume data D2 according to the image data D1 acquired by the acquisition unit 11. Any known technique can be used to identify the volume data D2. The volume data D2 may be the volume itself, or it may be data obtained by applying a predetermined correction process to the volume (for example, a value obtained by multiplying the volume by a coefficient). The identified volume data D2 is stored in the storage device 20.

[0024] Furthermore, head size correlates with body size, and brain size correlates with head size. Therefore, it is preferable that the identification unit 13 identifies standardized data of the volume of the right hippocampus-amygdala junction (right HATA) as volume data D2.

[0025] Specific methods for identifying volume data D2 include, for example, 1) analyzing raw hippocampal volume data directly, 2) analyzing the value obtained by dividing hippocampal volume by the body size of the brain and skull, and 3) using a "residue" method that removes shared variations such as brain volume, skull size, and height using multiple regression or ANCOVA. Factors such as gender and age can also be adjusted. The identification unit 13 can identify volume data D2 representing the volume of the hippocampal subfield (right hippocampal-amygdal junction (right HATA)) according to these methods.

[0026] The evaluation unit 15 evaluates the subject's emotional disorder according to the volume data D2 identified by the identification unit 13. Specifically, the evaluation unit 15 compares the volume data D2 identified by the identification unit 13 with reference data representing the volume of the right hippocampal-amygdala junction (right HATA) to evaluate the subject's emotional disorder status and risk of onset. For example, the subject's emotional disorder is evaluated according to the volume data D2 and data (hereinafter referred to as "preparation data") D3 representing the correlation between reference data and emotional disorder. The preparation data D3 is created in advance and stored in the memory device 20.

[0027] The reference data is data representing the volume of the right hippocampal-amygdal junction (right HATA) that has been previously identified for the subject (or other subjects). Then, for example, preparation data D3 is created by associating the evaluation of emotional disorder with this reference data. For example, the evaluation unit 15 identifies the evaluation corresponding to the volume data D2 in the preparation data D3 as the subject's emotional disorder. The evaluation unit 15 may be omitted from the emotional disorder evaluation system.

[0028] For example, the evaluation unit 15 can assess that if the volume of the right hippocampal-amygdal junction (right HATA) is small, the subject does not have an emotional disorder or has a low risk of developing an emotional disorder, and if the volume of the right hippocampal-amygdal junction (right HATA) is large, the subject has an emotional disorder or is at risk of developing an emotional disorder.

[0029] In one embodiment of the emotional disorder evaluation system 100, for example, the evaluation unit 15 evaluates that a subject has an emotional disorder or is at risk of developing one if the numerical value indicated by the volume data D2 from the identification unit 13 is above a set threshold. On the other hand, the evaluation unit 15 evaluates that a subject does not have an emotional disorder or is at low risk of developing one if the numerical value indicated by the volume data D2 is below a set threshold. Such thresholds can be appropriately set, for example, according to the correlation between reference data representing the volume of the right hippocampus-amygdala junction and emotional disorders. Furthermore, the thresholds may be set taking into account the characteristics and conditions of the subject.

[0030] In another embodiment of the emotional disorder evaluation system 100, for example, the evaluation unit 15 may evaluate the subject's emotional disorder based on the difference between previously measured volume data (A) of the same subject's right hippocampus-amygdala junction and newly measured volume data (B) of the right hippocampus-amygdala junction. For example, the subject's emotional disorder is evaluated by comparing the difference (absolute value) between volume data (A) and volume data (B) with a predetermined threshold. Such a threshold can be appropriately set, for example, according to the correlation between reference data representing the volume of the right hippocampus-amygdala junction and the emotional disorder. For example, if the difference between volume data (A) and volume data (B) is greater than the threshold, the evaluation unit 15 evaluates that the subject's emotional disorder has changed compared to before, and if the difference between volume data (A) and volume data (B) is smaller than the threshold, it evaluates that the change in the subject's emotional disorder state is small.

[0031] Furthermore, the evaluation unit 15 may evaluate that the subject's emotional disorder has worsened compared to before if volume data (B) is larger than volume data (A), and that the subject's emotional disorder has improved compared to before if volume data (B) is smaller than volume data (A).

[0032] Figure 2 is a flowchart of the process by which the emotional disorder assessment system 100 assesses a subject's emotional disorder. The process in Figure 2 is initiated, for example, in response to instructions from the administrator of the emotional disorder assessment system 100.

[0033] The acquisition unit 11 acquires image data D1 from the storage device 20 (Sa1). The identification unit 13 identifies volume data D2 representing the volume of the subject's right hippocampus-amygdala transition area according to the image data D1 acquired by the acquisition unit 11 (Sa2). The evaluation unit 15 evaluates the subject's emotional disorder according to the volume data D2 identified by the identification unit 13 (Sa3). Specifically, the emotional disorder is evaluated based on the correlation between the volume data D2 identified by the identification unit 13 and the emotional disorder.

[0034] Furthermore, the emotional disorder assessment system 100 may also include, for example, a memory unit for storing information regarding the volume of the right hippocampal-amygdala junction, and a display unit for displaying the volume of each hippocampal subfield.

[0035] The emotional disorder evaluation system 100 of the present invention can be used to evaluate the state (presence or absence and degree) of an emotional disorder in a subject, or the risk of developing an emotional disorder, based on the volume of the right hippocampal-amygdal junction (right HATA), and is highly objective and reliable.

[0036] The present invention is also specified as a method for creating data for evaluating emotional disorders in subjects (hereinafter referred to as the "data creation method").

[0037] Specifically, the data creation method includes the steps of acquiring image data D1 representing the subject's hippocampus and identifying volume data D2 representing the volume of the subject's right hippocampal-amygdal junction.

[0038] Here, volume data D2 may be the volume itself, as described above, or it may be data on which a predetermined correction process has been applied to the volume. Data on which a predetermined correction process has been applied to the volume refers to, for example, various forms of data relating to the volume of the right hippocampal-amygdal junction (right HATA) (such as numerical values ​​relating to the volume of the right hippocampal-amygdal junction (right HATA)). For example, using the volume data D2 identified by the data creation method of the present invention, a subject's emotional disorder can be evaluated based on the correlation between reference data representing the volume of the right hippocampal-amygdal junction (right HATA) and emotional disorder (preparation data D3).

[0039] The present invention can also be identified as a screening method for compounds having an effect of improving emotional disorders (hereinafter referred to as the "screening method").

[0040] Specifically, the screening method of the present invention includes a step of extracting compounds that reduce the volume of the right hippocampal-amygdala junction, using volume data representing the volume of this junction.

[0041] In the screening method of the present invention, for example, the emotional disorder evaluation system and data creation method of the present invention described above can be used. For example, the screening method of the present invention may include the steps of administering a candidate compound to a subject in a known manner, and obtaining volume data representing the volume of the right hippocampal-amygdal junction (right HATA) before and after administration. Furthermore, it may include the step of determining that a candidate compound that reduces the volume of the right hippocampal-amygdal junction after administration has an effect on treating emotional disorders. Compounds that reduce the volume of the right hippocampal-amygdal junction can be identified as active ingredients for emotional disorder treatment drugs.

[0042] Examples of such candidate compounds include small molecular weight chemical compounds, proteins, polypeptides, peptides, antibodies or their antigen-binding fragments, sugars, polysaccharides, polynucleotides, oligonucleotides, and lipids.

[0043] The emotional disorder evaluation system, data creation method, and screening method of the present invention are not limited to the embodiments described above.

[0044] Furthermore, the present invention is also specified as an evaluation method for evaluating the emotional disorder of a subject. Specifically, the evaluation method evaluates the emotional disorder of a subject based on the volume of the right hippocampus-amygdala junction of the subject. More specifically, for example, the volume data D2 described above is obtained, and the volume data D2 is compared with reference data representing the volume of the right hippocampus-amygdala junction to evaluate the state of the subject's emotional disorder and the effect of treatment. In addition, based on the volume of the right hippocampus-amygdala junction of the subject, [Examples]

[0045] Examples are shown below and explained in more detail, but the present invention is not limited to the following examples.

[0046] (Example 1) <1> Selection of healthy subjects Fifty-eight healthy subjects (mean age 25 ± 4.4 years, range 18–40 years, 31 males 24.5 ± 3.5 years, 27 females) participated. All subjects were right-handed based on the Edinpara handedness scale (Oldfield, 1971). Furthermore, none of the healthy subjects had any signs or history of neuropsychiatric disorders.

[0047] <2> Behavioral memory task The behavioral memory task involved presenting photographs one by one on a screen, in accordance with methods described in Patent Document 1, and asking participants to respond by pressing buttons for each photograph. There were three buttons, and participants were instructed to distinguish between photographs they were seeing for the first time (New), photographs that were the same as those seen in previous trials (Same), and photographs that were similar to but different from those seen in previous trials (Lure), and to press the corresponding button with a different finger (red button for New, blue button for Same, and green button for Lure).

[0048] The accuracy rate of the Lure task, a behavioral memory task, confirmed that hippocampal function was preserved in both healthy subjects and subjects with right temporal lobe diffuse astrocytoma. Figure 4 shows the BOLD signal (Blood Oxygen Level Dependent Signal) in the bilateral hippocampal-amygdal junction (HATA) of subjects with right temporal lobe diffuse astrocytoma, indicated by arrows.

[0049] <3> Acquisition of structural MRI Anatomical images were acquired using a 3 Tesla MRI scanner (Discovery MR750, GE Medical Systems, Waukesha, Wisconsin, USA) with a 32-channel head coil and advanced manual shimming to the temporal lobe. Anatomical three-dimensional (3D) T1-weighted images (an example of "image data") were acquired using a spoiled gradient recalled echo (SPGR) sequence with a high resolution of 1 mm slice thickness (matrix size 256 × 256, effective field of view 256 × 256 mm, repetition time 6.9 ms, echo time 3 ms, flip angle 15 degrees).

[0050] <4> Volume determination All T1-weighted and T2-weighted image data were processed using the freely available software Freesurfer (http: / / surfer.nmr.mgh.harvard.edu). Volume partitioning, including motion correction, skull removal, intensity normalization, white matter separation, gray matter / white matter 3D visualization (tessellation), and brain surface extraction, was identified using Freesurfer 6.0's fully automated reorganization ("recon-all"). Automated analysis of hippocampal and amygdala subfields was applied using a probabilistic atlas and a modified version of the Van Leemput algorithm (Van Leemput, et al., 2009). For the hippocampus, it was partitioned into subfields for each hemisphere. The hippocampal subfield, including the hippocampal tail, hippocampal base, anterior hippocampal base, parahippocampal base, Ammon's horn (CA)1, CA3, CA4, dentate gyrus granular cell layer (GC-DG), hippocampal molecular layer, hippocampal-amygdal junction (HATA), and fimbriae, was extracted.

[0051] For the reasons stated above, in order to evaluate brain structure alone, the volume of the hippocampal subfield, including the hippocampal-amygdal junction (HATA), was identified (an example of "volume data") following the procedure illustrated in Figure 3.

[0052] Then, to correct for brain volume, we calculated the total intracranial volume (TIV) estimated by Freesurfer6.0.

[0053] <5> result The results are shown in Figure 5. As shown in Figure 5, subjects with right temporal lobe diffuse astrocytoma had a larger volume of the right hippocampal-amygdal junction (right HATA) compared to healthy subjects and exhibited emotional disorders such as severe depression.

[0054] (Example 2) Twenty-seven healthy female subjects (mean age 25.5 ± 5.2 years, range 18–40 years, right-handed) were selected, and the volumes of the hippocampus and amygdala subfield were determined in the same manner as in Example 1. Similarly, the volumes of the hippocampus and amygdala subfield were also determined in women with emotional disorders.

[0055] The results are shown in Figures 6 and 7 and Table 1.

[0056] [Table 1]

[0057] As shown in Figures 6 and 7 and Table 1, the total cranial volume (TIV) of women with emotional disorders was significantly smaller than that of the healthy control group. On the other hand, the volume of the right hippocampal-amygdal junction (right HATA) in women with emotional disorders was 61.95 mm³. 3 The average value for the healthy control group was 57.89 mm. 3 It was significantly higher than [another value], and when compared using the ratio divided by TIV, it showed a significantly larger value.

[0058] Although not a solid organ, it was confirmed that women with emotional disorders had a significantly larger right hippocampal fissure (P<0.05) and a significantly smaller right hippocampal fimbria (P<0.05) compared to healthy control groups. Therefore, the right hippocampal fissure and right hippocampal fimbria, like the hippocampal-amygdal junction (right HATA), can be used as indicators for evaluating emotional disorders.

[0059] As described above, it was confirmed that the volume of the right hippocampal-amygdal junction in subjects can be identified, and that the subject's emotional disorder can be evaluated based on this identified volume. Furthermore, it was confirmed that by using volume data representing the volume of the right hippocampal-amygdal junction and using the reduction of this volume as an indicator, compounds that have an effect on improving emotional disorder can be screened. [Explanation of Symbols]

[0060] 10: Control device 11: Acquisition part 13: Specific part 15: Evaluation Department 20: Storage device 100: Emotional Disorder Assessment System

Claims

1. An acquisition unit that acquires image data representing the subject's hippocampus, A unit for identifying volume data representing the volume of the right hippocampal-amygdal junction of a subject, based on the aforementioned image data, An evaluation unit evaluates the subject's emotional disorder in accordance with the correlation between the volume data identified by the specified unit, reference data representing the volume of the right hippocampus-amygdala transition area, and the emotional disorder. An emotional disorder assessment system equipped with the following features.

2. The evaluation unit evaluates that the subject has an emotional disorder or is at risk of developing an emotional disorder if the numerical value indicated by the volume data is above a set threshold. If the numerical value indicated by the volume data is below a set threshold, the subject is evaluated as not having an emotional disorder or having a low risk of developing an emotional disorder. The emotional disorder evaluation system according to claim 1.

3. The evaluation unit evaluates the subject's emotional disorder based on the difference between the previously measured volume data (A) of the subject's right hippocampus-amygdala junction and the newly measured volume data (B) of the right hippocampus-amygdala junction. The emotional disorder evaluation system according to claim 1.

4. A screening method for compounds that have an effect of improving emotional disorders, The process includes a step of extracting compounds that reduce the volume of the right hippocampus-amygdala transition zone, using volume data representing the volume of the said zone. Screening methods.

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