BIPLONG - The Bipolar Disorder in the Longitudinal Course (BIPLONG)

The Bipolar Disorder in the Longitudinal Course- Genom-wide Analysis of the genotype1 - phenotype2- Relationships in the Longitudinal Course of Psychosis

The BIPLONG (The Bipolar Disorder in the Longitudinal Course ) study is a longitudinal study on the course of bipolar disorders and comprises two sub-studies: On the one hand, BIPLONG examines the genetic foundation and change in bipolar disorder, on the other hand, metabolic changes, clinical symptoms and cognition in bipolar disorders is evaluated. A current subproject of BIPLONG is the analysis of the psychological response of the COVID-19 (Corona virus disease) pandemic. With the parameters examined in BIPLONG, it is hoped to gain better understanding of the bipolar disorder in the longitudinal course.

Study Overview

• Status: Recruiting
• Conditions: Bipolar Disorder

Detailed Description

Study Procedure:

In addition to the bipolar patients, healthy controls will also be included. The same inventories will be used for the control subjects and the same examinations or visits will be performed; bipolar-specific disease questions will not be asked in controls.

Intervention: Longitudinal study

Method:

All patients and controls undergo several assessments every six months:

Blood samples are collected with the following main parameters of interest being examined:

• Collection and analysis of DNA, establishment of permanent cell lines, determination of mRNA and gene products (proteins), proteomics, lipidomics.
• Routine parameters: Blood count, TSH, T3, T4, homocysteine, creatinine, amylase, lipase, CK, urea, uric acid, coagulation, HBA1c, glucose, lipids (triglyceryl, LDL, HDL, cholesterol, mass spectrometry), transaminases, CRP- levels, vitamin D.
• Biomarkers: oxidative stress parameters and antioxidants, neuroinflammatory markers (e.g. interleukins, tumor necrosis factor, interferons, GDNF, VEGF, etc.), neurotrophins (BDNF, NT, Trk..), insulin, IGF, adipokines, Apo-E and AAT analysis, tryptophan/kynurenine metabolites
• Intestinal hormones grehlin, glucagon-like peptides 1 and 2 (GLP-1/2) and cholecystokinin

Additionally, socio-demographic data and psychological data are collected by administering self-assessment questionnaires. Further, neurocognitive tests are administered.

The current psychological and psychiatric state of all subjects is examined by external ratings done by experts.

Anthropomethric measures are examined (waist-to-hip ratio, blood pressure, weight, height).

Additionally, MRI is conducted on all subjects (for patients every 6 months, for controls every 12 months).

Primary hypothesis:

• Gene-environment interactions are significantly contributory to bipolar affective disorder.
• There are pathologically altered neurobiological markers that play a role in the pathogenesis of bipolar disorder.
• There is an influence of anthropometric data on the course of bipolar disorder.

Statistical analysis and anticipated sample size:

Baseline data analysis will be investigated using a multi-factorial between subject design, with the variables of group (bipolar patients versus healthy controls), gender (males versus females), weight (normal weight versus overweight), etc. as independent factors, depending on the research question. As dependent variables, in addition to sociodemographic and clinical variables (number of episodes, etc.), physiological parameters (blood parameters, anthropometry and lipometer data, EEG, ECG, MRI) and psychological variables (psychological questionnaires) will be investigated. Likewise, covariates such as age or body mass index will be included as needed.

Correlation analyses (bivariate, partial) should show possible correlations between the variables. Discriminant analyses should find out which variable best separates the investigated groups (e.g. patients vs. controls). Furthermore, regression analyses (linear, multiple) will be performed to obtain additional information about the predictive value of the variables under investigation. All analyses will be computed using IBM SPSS Statistics 20.

For the "a priori analysis" of the follow-up study (T1-T5), a repeated measures design (repeated measures within factors) was adopted. The case number calculation (effect size d between .30 and .80; Cohen, 1988) for the F-test thus results in a sample size of 47 patients with a target effect size of .40 (power 95%; alpha .05; calculated with GPower 3.1). The correlation analyses at the first measurement time point (power .95, alpha .05, effect size: .35) yields 79 subjects per group (Pat. vs. controls) at all time-points.

• Study Type: Observational
• Enrollment (Anticipated): 560

Contacts and Locations

• Study Contact: Name: Eva Reininghaus, MD, PhD, MBA; Phone Number: +43 316 385 80968; Email: eva.reininghaus@medunigraz.at
• Study Contact Backup: Name: Nina Dalkner, PhD, MSc; Phone Number: +43 316 385 30081; Email: nina.dalkner@medunigraz.at

Study Locations

• Austria
  • Styria
    • Graz, Styria, Austria, 8036
      • Recruiting
      • Medical University Graz
      • Contact: Eva Reininghaus, MD, PhD, MBA; Phone Number: +43 316 385 80968; Email: eva.reininghaus@medunigraz.at
      • Contact: Nina Dalkner, PhD, MSc; Phone Number: +43 316 385 30081; Email: nina.dalkner@medunigraz.at

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients with bipolar disorder and healthy controls within the age frame of 18-75 are included.

Description

Inclusion criteria:

• Pat. with bipolar disorder, with an age between 18 and 85 years.
• Euthymic/ maximum mildly depressed at the time of consent (for this, the severity of depression will be determined using the Hamilton Depression Scale, this will also be included in any calculations).

Exclusion criteria:

• Pat. refuses participation
• Currently severely depressed/manic episode at the time of consent
• Other currently active severe mental/ brain organic disease (epilepsy, brain tumor..)
• St.p. severe craniocerebral trauma/ brain surgery.
• Reduced intelligence (IQ< 70)
• Moderate/ severe dementia (Mini Mental Status Examination, MMSE, 20 and above)
• Clearly substance-induced clinical picture

Inclusion criteria healthy controls:

• For the whole procedure, made controls (age, gender) are needed. For this purpose we recruit controls by word of mouth or ask relatives of bipolar patients if they would like to participate. Patients are tested for the presence of a possible mental illness using Mini-DIPS (Diagnostisches Interview bei psychischen Störungen)
• Inclusion criteria: 18-75 years, no severe mental illness (depression, mania, psychosis; severe anxiety or obsessive-compulsive disorder requiring treatment, addictive disorder other than nicotine).

Exclusion criteria:

• First-degree relatives with severe mental illness.
• Severe active drug dependence (i.e. alcohol, benzodiazepines morphines)
• Current major depressive/ manic episode
• Other currently active severe mental/ brain illness (epilepsy, brain tumor..)
• St.p. severe craniocerebral trauma/ brain surgery.
• Congenital/ early childhood acquired intelligence impairment
• Moderate/ severe dementia (from MMSE 20)

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Patients; Patients with the Diagnosis of a Bipolar Disorder
Healthy Controls; Individuals with no diagnosis of Bipolar Disorder

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CVLT- california verbal learning test	The California Verbal Learning Test (CVLT) provides a brief and individualized assessment of verbal learning strategies and processes. The higher the score, the better the outcome	at six months
STROOP Farbe-Wort-Interferenz-Test (FWIT)	As an objective and reliable multidimensional performance test, the Color-Word. The Interference Test measures elementary information processing skills (selection, encoding, and decoding) in the visual-verbal functional domain. The lower the score, the better the outcome.	at six months
D2-R	To measure the subject's ability to concentrate and the speed and accuracy in distinguishing similar visual stimuli. The higher the score, the better the outcome.	at six months
"Reading the eyes of the mind" =Theory of mind	measurement of the ability to detect social cues. The higher the score, the better the outcome.	at six months
Trail Making Test A/B, TMT-A	Measurement of cognitive processing speed, as well as linguistic, executive, and attentional components. The lower the score, the better the outcome.	at six months
Mehrfachwahl Wortschatz Test (MWT-B)	Measurement of the general intelligence level. The higher the score, the better the outcome.	at six months
Number Symbol Test	Measurement of processing speed. The higher the score, the better the outcome.	at six months
Number Repeat	Measurement of working memory. The higher the score, the better the outcome.	at six months
Beck Depressions Inventar II (BDI-II)	Measurement of depression severity; 21 items on a scale of 0-3 (ascending). The higher the score, the worse the outcome.	at six months
Manie-Selbstbeurteilungsskala (MSS) (self-rating scale)	Measurement of manic symptoms; 48 items (dichotomous). The higher the score, the worse the outcome.	at six months
Questionnaire of religiosity	socio-demographic assesment of religiosity; 2 items.	at six months
Big Five Inventory-10 (BFI-10)	Measurement of personality variables; 10 items on a scale of 1-5 (ascending).	at six months
World Health Organisation Quality of Life (WHOQOL Bref)	Measurement of life-quality and health; 26 items on a scale of 1-5 (ascending).	at six months
Life Event Questionnaire (LEQ)	Measurement of life events and their influence; 79 items on a scale of 0-3 (ascending)	at six months
Temperament and affective disorders (TEMPS-A)-Scale	35 items on a scale of 1-5 (ascending). The higher the score, the better the outcome.	at six months
Brief symptom inventory (BSI)	Measurement of psychological symptoms; 53 items on a scale of 0-4 (ascending). The higher the score, the worse the outcome.	at six months
Anhedonia scale (AS)	Measurement of Anhedonia; 14 items on a scale of 1-4 (ascending). The higher the score, the worse the outcome.	at six months
Maslach Burnout Inventory (MBI-GS-D)	Measurement of burnout symptoms; 16 items on a scale of 1-6 (ascending). The higher the score, the worse the outcome.	at six months
Resources in Sexuality and Partnership (RSP)	Measurement of relationship emotions; 25 items on a scale of 1-5 (ascending).The higher the score, the better the outcome.	at six months
Satisfaction in the couple relationship (ZIP)	Measurement of relationship satisfaction; 7 items on a scale of 1-5 (ascending), 3 items open questioned. The higher the score, the better the outcome.	at six months
Demographic Data	Measurement of demographic data	at six months
Questionnaire of current life situation	Measurement of demographic and diagnostic data;	at six months
Anthropometric Data - weight	Measurement of weight	at six months
Anthropometric Data- height	Measurement of height	at six months
Anthropometric Data - waist-to-hip ratio	Measurement of waist-to-hip ratio	at six months
Anthropometric Data - blood pressure	Measurement of blood pressure	at six months
Clinical Global Impression (CGI)	External rating of a symptom severity; 2 items on a scale of 0-7 (ascending). The higher the score, the better the outcome.	at six months
Global Assessment Scale of Functioning (GAF)	External rating of level of functioning; 1 item on a scale of 1-100 (ascending). The higher the score, the better the outcome.	at six months
Hamilton Depression Scale (HAMD)	External rating of depression symptoms; 21 items on a scale of 0-4 (ascending).The higher the score, the worse the outcome.	at six months
Young Mania Rating Scale (YMRS)	External rating of manic symptoms; 11 items on a scale of 0-4/0-8 (ascending). The higher the score, the worse the outcome.	at six months
Specific Level of Functioning Assessment and Physical health Inventory (SLOF)	External rating of functioning; 43 items on a scale of 1-5 (ascending), 2 items open questioned. The higher the score, the better the outcome.	at six months
Supplementary Data for External Rating	External rating of bipolar symptoms; 7 items.	at six months

Collaborators and Investigators

• Sponsor: Medical University of Graz

Study record dates

Study Major Dates

• Study Start (Actual): June 13, 2013
• Primary Completion (Anticipated): June 13, 2022
• Study Completion (Anticipated): June 13, 2022

Study Registration Dates

• First Submitted: September 14, 2021
• First Submitted That Met QC Criteria: September 23, 2021
• First Posted (Actual): October 1, 2021

Study Record Updates

• Last Update Posted (Actual): October 1, 2021
• Last Update Submitted That Met QC Criteria: September 23, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Bipolar and Related Disorders; Bipolar Disorder
• Other Study ID Numbers: 25-355 ex 12/13

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No