Brain Diseases

The study design and protocol have been approved by the ethics committees for human research at our institute (IRB number: R2019-227). This study followed a prospective and observational design. The study was performed in accordance with the approved guidelines of the Declaration of Helsinki. From November 2020 to February 2022, 133 healthy volunteers aged ≥ 20 years underwent MRI after providing written informed consent explaining the potential for detection of brain disease. Volunteers were recruited from medical staff and students, and their families by open recruitment. Inclusion criteria for this study were those who had no history of brain injury, brain tumor or cerebrovascular disease on previous brain MRI, or those who had never undergone brain MRI and no neurological symptoms including cognitive function. One volunteer aged 84 years old was excluded from this study because of a history of head surgery due to a head injury over 30 years ago. In addition, three volunteers were incidentally found small unruptured intracranial aneurysms with a maximum diameter of < 2 mm on this MRI. They were included in this study, because small unruptured aneurysms might not affect CSF motion.
Patients’ MRI data was used in an opt-out method, after their personal information was anonymized in a linkable manner. Among 44 patients suspected with NPH, 5 patients diagnosed with secondary NPH [29 (link)] that developed after subarachnoid hemorrhage [3 (link)], intracerebral hemorrhage [1 (link)], and severe meningitis [1 (link)], and 3 patients diagnosed with congenital/developmental etiology NPH [30 (link)] were excluded from this study. Finally, 36 patients diagnosed with iNPH who had radiological findings of disproportionately enlarged subarachnoid space hydrocephalus (DESH) [31 (link)], specifically ventricular dilatation, enlarged Sylvian fissure, and narrow sulci at the high convexity, and triad symptoms of gait disturbance, cognitive impairment, and/or urinary incontinence were included in this study, according to the Japanese guidelines for management of iNPH [32 (link)]. Of them, 18 patients (50%) underwent CSF removal in 30–35 ml via a lumbar tap and were evaluated for changes in their symptoms before, one day and two days after the CSF tap test. In addition, 21 patients (86%) underwent CSF shunt surgery and their symptoms improved by ≥ 1 point on the modified Rankin Scale and/or the Japanese iNPH grading scale [32 (link)].

A total of 62 participants (38 women and 24 men) were examined in this study. Of these, 31 patients fulfilled the criteria of OCD [ICD-10 F42.X: mean age 35.2 (SD = 10.7) years] and 31 subjects formed the healthy control group [mean age 39.1 (SD = 15.0) years]. A detailed description of the groups can be found in Table 1.Table 1

Sociodemographic and clinical characteristics

Trait	OCDN = 31	HCN = 31	p-value*
Age, mean (SD), years	38,7 (11,9)	39,6 (13,1)	n. s
Gender
Female n,	19 (61,3%)	19 (61,3%)	n. s
Male n,	12 (38,7%)	12 (38,7%)
Marital status
Single, n	17 (54,8%)	12(38,7%)
Married, n	9 (29,0%)	19 (61,3%)	p = 0.009
Divorced, n	5 (16,1%)	0
Current Partnership
- No	13 (41,9%)	7 (22,6%)	n. s
- Yes	18 (58,1%)	24 (77,4%)
Graduation
High school, n	25 (80,7%)	24 (77,4)
Junior high school, n	3 (9,7%)	5 (16,1%)	n. s
Low school., n	3 (9,7%)	2 (6,5%)
Occupational status
Current employment (Including be a student), n	22 (71,0%)	27 (87,1%)	n. s
No current Job,	9 (29,0%)	4 (12,9%)
Diagnosis (ICD-10)
F42.0, n	5 (16,1%)	/
F42.2, n	26 (83,9%)
Age of onset
mean (SD), years	23,2 (9,1)	/
Duration of illness
mean (SD), years	15,8 (10,8)	/

^*x²-Test/ t-Test; n. s. non-significant, OCD Obsessive–compulsive disorder, HC Healthy controls

All OCD patients were recruited and examined during their treatment at the Department of Psychiatry (LWL-University Hospital of the Medical Faculty of Ruhr-University Bochum, special outpatient clinic for OCDs). Examination of the healthy volunteers also took place at the LWL-University Hospital Bochum and recruitment was via notices and flyers.
Patients and healthy volunteers aged 18–67 years were included. Further inclusion criteria were a verbal IQ > 70, sufficient German language skills and the ability to give informed consent according to the Helsinki and ICH-GCP declarations. Exclusion criteria for the study were: severe somatic diseases; other mental diseases, such as reduced intelligence (ICD10 F70–F70.9), schizophrenia (ICD10 F20–F20.9) or organic brain disorders (ICD10 F06–F06.9, dependence on illegal drugs); acute suicidal tendencies or behaviour endangering others; and lack of informed consent to participate in the study.
Furthermore, psychopharmacotherapy was not an exclusion criterion for patients with OCD. In this respect, 96.8% of the patients (n = 30) received monotherapy, whereby antidepressants from the selective serotonin reuptake inhibitor group [e.g. sertraline (n = 21), escitalopram, paroxetine, fluoxetine] but also clomipramine (a tricyclic antidepressant) were predominantly used. Moreover, seven of the patients received a combination treatment (mainly a sedating antipsychotic medication, e.g. promethazine or quetiapine). At the time of inclusion in the study, 12 patients were receiving psychotherapeutic treatment (validation therapy: n = 9; deep psychology: n = 3). Only five of the patients (16.1%) with OCD had not received psychotherapy at the time of study inclusion, either currently or in the past. A detailed anamnesis was taken from all OCD patients and healthy volunteers in a semi-structured interview (duration 45–60 min). The psychometric characteristics, including shame and guilty proneness, were gathered using various questionnaires.
The study was approved by the local Ethics Committee (No. 20–6883) of the Medical Faculty of Ruhr-University Bochum.

The study population comprised three subpopulations; (1) Patients diagnosed with schizophrenia less than 2 years before inclusion in the study (patients diagnosed with SCZ < 2), (2) Psychiatric healthy controls (PHC) with no history of mental illness matched to patients diagnosed with SCZ < 2 on age, sex, and smoking status (smoker/non-smoker) at the time of inclusion, and (3) Patients diagnosed with schizophrenia 10 or more years before inclusion (patients diagnosed with SCZ ≥ 10). Patients with schizophrenia were recruited from the North Denmark Region. Only patients 18 years or older at inclusion diagnosed with schizophrenia or schizo-affective disorder (ICD-10 F20 or F25) and being able to give written informed consent, were included in the study. In Denmark, schizophrenia is defined according to ICD-10, which lists first-rank symptoms, delusions of bizarre characteristics or a combination of at least two of the following symptoms: hallucinations on a daily basis combined with delusions, catatonia, negative symptoms or disorganized thinking.
First-rank symptoms include auditory hallucinations commenting or conversing, somatic hallucinations, thought withdrawal or thought broadcasting. The presence of a brain disorder, drug intoxication or withdrawal hinder the diagnosis of schizophrenia.Patients were excluded if pregnant, breastfeeding or if they were unable to participate in the planned program for the primary cohort study [13 (link)].
Using a random recruitment approach, psychiatrically healthy controls were matched on age, sex, and smoking status to patients diagnosed with SCZ < 2. They were invited to participate in this comprehensive cardiac screening programme.
The clinical prospective cohort study has been approved by The North Denmark Region Committee on Health Research Ethics (N-20140047) and is consistent with the ethical standards of the Declaration of Helsinki 2013. The personal data categories collected by the project has been registered in the processing activities of research in the North Denmark Region in compliance with the European Union’s GDPR article 30.