Genome Wide Association Studies in PsychiatryDr.Guru S Gowda
Neuropsychiatric and neurodevelopmental disorders are multifactorial in origin with multiple genetic determinants and its interaction with others resulting in clinically diverse phenotypes. Affected individuals harbour different risk alleles in a heterogeneous genetic background that make candidate disorder genes difficult to detect via studies. One such effort to find the influence of genetic factors is Genome Wide Association Study (GWAS), which is an approach to identify common genetic variations like Single-Nucleotide Polymorphism (SNP) and Copy Number Variation (CNV) associated with a disease / traits. It is a powerful method for such investigations, particularly by enabling the integrated analysis of SNPs and CNVs. There are now hundreds of candidate genes with DNA copy number variations or single nucleotide polymorphisms (SNPs) characterised from clinically diagnosed individuals.
With more mature molecular and statistical methods, we are entering a new era of Network and Pathway Analyses. This may reveal coherent biological processes contributing to psychiatric illnesses but the evidence is limited to date.
This seminar aims at providing a broad overview on GWAS - History, approach to G W A S, GWAS studies in Psychiatry and its Implication, complex network and pathway analysis concepts, current challenges etc, and ends with conclusion and future directions.
This is a presentation done on 4/6/11 for the Grand Rounds at Wayne State university by Pallav Pareek M.D.
This presentation talks about the concept of prdrome as it is(if?) applicable to schizophrenia, and if schizophrenia is becoming more of a preventable illness as science progresses. If so what are the various ways and means in which we can accomplish this prevention.
Amidst so much controversy on the issue , whether there is a prodrome for this illness or not, here I have tried to present the recent advances in this field and the recent scientific literature in this regard.
Genome Wide Association Studies in PsychiatryDr.Guru S Gowda
Neuropsychiatric and neurodevelopmental disorders are multifactorial in origin with multiple genetic determinants and its interaction with others resulting in clinically diverse phenotypes. Affected individuals harbour different risk alleles in a heterogeneous genetic background that make candidate disorder genes difficult to detect via studies. One such effort to find the influence of genetic factors is Genome Wide Association Study (GWAS), which is an approach to identify common genetic variations like Single-Nucleotide Polymorphism (SNP) and Copy Number Variation (CNV) associated with a disease / traits. It is a powerful method for such investigations, particularly by enabling the integrated analysis of SNPs and CNVs. There are now hundreds of candidate genes with DNA copy number variations or single nucleotide polymorphisms (SNPs) characterised from clinically diagnosed individuals.
With more mature molecular and statistical methods, we are entering a new era of Network and Pathway Analyses. This may reveal coherent biological processes contributing to psychiatric illnesses but the evidence is limited to date.
This seminar aims at providing a broad overview on GWAS - History, approach to G W A S, GWAS studies in Psychiatry and its Implication, complex network and pathway analysis concepts, current challenges etc, and ends with conclusion and future directions.
This is a presentation done on 4/6/11 for the Grand Rounds at Wayne State university by Pallav Pareek M.D.
This presentation talks about the concept of prdrome as it is(if?) applicable to schizophrenia, and if schizophrenia is becoming more of a preventable illness as science progresses. If so what are the various ways and means in which we can accomplish this prevention.
Amidst so much controversy on the issue , whether there is a prodrome for this illness or not, here I have tried to present the recent advances in this field and the recent scientific literature in this regard.
The association of neuropsychiatric disorders with cerebrovascular disease has been recognized by clinicians for over 100 years. Disease of the vascular system contribute greatly to the sum total of psychiatric disability, chiefly in the elderly population, mainly as a result of stroke, cerebrovascular accidents & subarachnoid haemorrhage.
Classification in Psychiatry
The concept, reliability, validity, advantages and disadvantages of different classification systems, controversies in psychiatry classification
The association of neuropsychiatric disorders with cerebrovascular disease has been recognized by clinicians for over 100 years. Disease of the vascular system contribute greatly to the sum total of psychiatric disability, chiefly in the elderly population, mainly as a result of stroke, cerebrovascular accidents & subarachnoid haemorrhage.
Classification in Psychiatry
The concept, reliability, validity, advantages and disadvantages of different classification systems, controversies in psychiatry classification
The video for this presentation is available on our Youtube channel:
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Provides a high-level overview of the main feel-good chemicals, practical and pharmacological ways to address chemical imbalances and how chemical imbalances can trigger a relapse.
Serotonin is major neurotransmitter and affects the physiology of our body. Serotonin antagonists are used in various pathological conditions of body. This is a small presentation showing feature of serotonin.
The video for this presentation is available on our Youtube channel:
https://youtube.com/allceuseducation A continuing education course for this presentation can be found at https://www.allceus.com/member/cart/index/index?c=
AllCEUs provides counseling education and CEUs for LPCs, LMHCs, LMFTs and LCSWs as well as addiction counselor precertification training and continuing education.
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Addiction as a brain disease Brain Imaging in AddictionsRiverMend Health
Gene-Jack Wang, M.D.-
Member, RiverMend Health Scientific Advisory Board for Addiction & Psychiatry
Professor of Radiology, Stony Brook University
Sr. Scientist, Bioscience Department, Brookhaven National Laboratory.
Dr. Gene Wang addresses the RiverMend Heath Scientific Advisory Board on addiction as a brain disease as well as comparing and analyzingy brain scans of addicts to those of non addicts.
To watch lecture: http://vimeo.com/97724513
For more information visit: http://www.rivermendhealth.com/scientific-advisory-board-addiction.html
GENETIC BASIS OF PSYCHIATRIC DISRODERS AND THE RELEVANCE OF CLINICAL PRACTICEPRASHNATH javali
Presentation regarding the counseling of genetic disorders and the steps involved along with the process of Genetic counseling guidance,way to disclose the results,steps to be taken for the care of mentally ill persons.
This presentation summarises the importance of genetics in epilepsy, whom to test, and the various tests available. It looks at the role of genetics in various forms of epilepsy and recent advances in precision medicine.
Schizophrenia is a serious mental illness that affects how a person thinks, f...AmitSherawat2
Schizophrenia is a serious mental illness that affects how a person thinks, feels, and behaves. People with schizophrenia may seem like they have lost touch with reality, which can be distressing for them and for their family a
Schizophrenia is one of the most debilitating mental illness which demands immediate attention by the family. There are certain types of schizophrenia based on its symptom presentation and its management mostly depends sxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx
Running head SCHIZOPHRENIA MENTAL DISORDER .docxtoltonkendal
Running head: SCHIZOPHRENIA MENTAL DISORDER 1
SCHIZOPHRENIA MENTAL DISORDER 2
Schizophrenia Mental Disorder
Student’s Name
Course Name
Instructor’s Name
University Affiliation
Schizophrenia Mental Disorder
Introduction
Schizophrenia is a type of psychological illness. It is a chronic and unembellished mental disorder that mainly distresses an individual’s thinking, norms as well as to their extent of sensation. According to modern day research, reports indicates that persons who have schizophrenia might appear as if they have misplaced touch with realism. However, much it is not collective as in comparison with the other mental disorders, its symptoms seem to be much disabling in nature (Miller, 2012). An example is a reduction of a person’s pleasure in their daily undertakings. It raises the question; what can a man do in the absence of desire and affection in all their doings? From the information as already mentioned above, this paper takes turn providing an enhanced analysis of the mental disorder disease – Schizophrenia.
Signs and Symptoms
In close to all the reported cases, signs and symptoms of schizophrenia often start from ages ranging between 16 and 30. There are however fewer cases that the disease has identification among the children. In this paper, it classifies the symptoms and signs into three categories. They include the positive, negative, as well as to the cognitive symptoms as illustrated below.
Positive signs:
In this category, they have a regard for psychotic norms. It means that it is hard to depict the signs commonly in people who are living a healthy lifestyle. However, the given individuals might tend to part ways with their connectivity with different components of reality. The symptoms might include: -
· Delusions
· Agitated movements of the body in a disorderly manner
· Hallucinations
· Unfamiliar perspective of thinking entailing disorderly thoughts and imaginations
Negative symptoms:
In this set, symptoms have a closer affiliation with disturbances to both the common behaviors as well as to particular emotions (Mueser, 2011). The symptoms comprise of: -
· Condensed level of speaking
· Reduction in the extent of both pleasure and feelings in a person’s everyday life undertakings
· Decline on the voice tone as well as the ordinary portrayal of emotions
· Hardships in commencing and sustaining of various activities
Cognitive symptoms:
In this set of symptoms, it varies from one given an individual to the other. To certain people, the symptoms are observable as being delicate in nature. On the other hand, the symptoms prove to be extra severe (Weiberger et al., 2011). In such situations, the affected persons are capable of recognizing alterations in either the facets of thinking and imagination, as well as to variations in their memory. Examples of symptoms ...
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
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disorder called alcohol use disorder (AUD), with mild, moderate,
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In the DSM-5, all types of substance abuse and dependence have been
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Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
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New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
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4. • The symptoms of schizophrenia can be categorized
into three wide-ranging groups.
1. Positive symptoms
2. Negative symptoms
3. Cognitive symptoms
Symptoms
5. Symptoms
• Positive symptoms include: hallucinations
(visual and auditory), delusions, and racing
thoughts.
• Negative symptoms include: apathy, lack of
emotion, and poor social functioning.
• Cognitive symptoms include: disorganized
thoughts, difficulty concentrating or
completing tasks, and memory problems.
6. Positive and Negative Symptoms
Negative Positive
A logia (abnormal speech) Hallucinations
Lack of interest in life Delusions
Poor in making decisions Bizarre behavior
Languages impairment Unusual thoughts
Social isolation Disorder of movement
7.
8. • No one knows the exact causes of Schizophrenia, but
multiple possible factors have been discovered.
• These factors include:
1. Genetics
2. Brain chemical imbalance
3. Environmental factors
4. Family history
Causes
9. Etiology of Schizophrenia
• The etiology(causes) and pathogenesis of
schizophrenia is not known
• It is accepted, that schizophrenia is „the
group of schizophrenias“ which origin is
multifactorial:
– internal factors : genetic, inborn, biochemical
– external factors : trauma, infection of CNS,
stress
10.
11. Genetic predisposition
Neurodevelopmental abnormalities and target features
Further brain dysfunction and schizophrenia
Neurodegeneration and schizophrenia
Etiologic pathway
Early environmental insults
Later environmental insults
psychosis
12. Affects 1 %1 % of the general population.
8% in siblings of affected subjects.
12% in offsprings of one affected parent.
40% in offsprings of two affected parents.
47% in subjects of affected monozygotic twins.
Epidemiology
15. What is known about the inheritance pattern of
schizophrenia?
• Although results from family, twin, and adoption studies provide
overwhelming evidence that genetic factors play a part in the cause of
schizophrenia, the exact mechanisms of genetic transmission remain
unidentified.
• Despite the genetic and phenotypic complexity of schizophrenia, much
progress has been made.
• Research has largely excluded the possibility that genes of major effect
exist; linkage analysis has provided independently replicated evidence for
genes of moderate effect on several chromosomal regions.
• Association studies suggest that alleles of at least two genes, those
encoding D3 and 5HT 2A, confer a small rise in susceptibility to
schizophrenia, and there are convergent findings from several different
lines of research implicating regions such as 22q11, although no specific
causative genes for schizophrenia have been definitively identified yet.
16. What genetic testing could you offer this
couple?
• Predictive genetic testing is unlikely to be useful in the
near future except for some rare pedigrees if a single
major locus is identified.
• One area where genetic testing may be more helpful,
however, is schizophrenia associated with VCFS.
• In most cases, the deletion of 22q11 occurs as a de novo
mutation, but in 10% of those affected, it is inherited from
a parent, who may have a mild presentation of the
syndrome .
• In such cases, parents could be tested for the deletion,
and, if confirmed, testing could be offered to siblings,
especially if other clinical features are present.
20. family studies
• As can be seen from the graph below, schizophrenia definitely has a very
significant genetic component.
• Those who have a third degree relative with schizophrenia are twice as
likely to develop schizophrenia as those in the general population.
• Those with a second degree relative have a several-fold higher incidence of
schizophrenia than the general population, and first degree relatives have
an incidence of schizophrenia an order of magnitude higher than the
general populace.
• Following are two images that summarize the average risks for developing
schizophrenia for different groups of people.
• (The statistics in the two images vary slightly due to inclusion of different
study data).
29. If we were to summarize all of these data on an ideogram of the human
genome, they might look like this; to the right of the chromosome is an "S" for
schizophrenia susceptibility, a "B" for bipolar, and an asterisk (*) where both
types of disorders are mapped to the same location.
56. Genetics of Scizophrenia :DNA
variation
• Evidence for a substantial genetic contribution comes from family, twin and
adoption studies but the underlying causes and pathogenesis of the
disorder remains unknown.
• The past few years have witnessed marked progress in our understanding
of genetic risk at the level of DNA variation, which has been largely driven
by applying advanced genomic technologies to very large samples.
• There is evidence that risk variants occur across the full allelic frequency
spectrum, many of which are associated with other neuropsychiatric
disorders.
• Moreover, genetic associations involving different classes of mutations have
now implicated specific biological pathways in disease pathogenesis.
57. recent advances in schizophrenia genetics
• de novo mutation,
• rare copy number variation (CNV),
• rare single nucleotide variant (SNV, defined as point
mutations with a frequency less than 1%)
• and small insertion/deletion (indel) mutations
• and single nucleotide polymorphisms (SNPs, defined as
point mutations with a frequency greater than 1%)
62. • Abnormal production or reaction to the important
chemical neurotransmitter dopamine and maybe
others.
• Dopamine is responsible in sending messages
through the brain and effects how the brain
perceives things.
• Imbalance between dopamine and serotonin.
Brain chemical imbalance:
66. DOPAMINE HYPOTHESIS
The Dopamine hypothesis states that the
brain of schizophrenic patients produces
more dopamine than normal brains.
–Evidence comes from
–studies with drugs
–post mortems
–pet scans
67. Normal Level of
Dopamine In The
Human Brain
Elevated Level of
Dopamine In The Brain of
a Schizophrenic Patient
(specifically the D2
receptor)
Neurons that use the transmitter ‘dopamine’ fire too often and transmit
too many messages or too often.
Certain D2 receptors are known to play a key role in guiding attention.
Lowering DA activity helps remove the symptoms of schizophrenia
68. Etiology of Schizophrenia - Neurodevelopment
Model
• Neurodevelopmental model supposes in
schizophrenia the presence of “silent lesion” in the
brain, mostly in the parts, important for the
development of integration (frontal, parietal and
temporal), which is caused by different factors
(genetic, inborn, infection, trauma...) during very
early development of the brain in prenatal or early
postnatal period of life.
69. • Stress inducing environmental factors such as
social pressure, physical or sexual abuse, loss of
loved ones, hormones, malnutrition, and early
exposure to viruses.
• The major brain changes that occur during
puberty has also been identified as a possible
contributing factor.
Environmental factors
70. TABLE 1. Single-Nucleotide Polymorphisms (SNPs) in 33 Genes
Assayed in 130 Families and Associated With Schizophrenia or
Related Phenotypes in Previous Studies
Gene SNP Identifiers Associated (p<0.01) With at
Least One Endophenotype in
Current Study
ADRBK2a
rs576895, rs558934, rs5761116
AKT1a
rs2494732, rs1130214 rs2494732b
BDNF rs6265
CACNG2a
rs2267341, rs2283981,
rs738518
CHRNA7 rs3087454
COMTa
rs737865, rs4680
DAOa
rs2070587, rs3741775
DAOAa
rs1341402, rs239119, rs778294
DGCR2a
rs2072123, rs807759
DISC1 rs3738401, rs2793092,
rs2793091, rs2492367,
rs1000731, rs821597,
rs4658971, rs843979, rs821616
rs821597b
, rs843979
71. Gene SNP Identifiers Associated (p<0.01) With at Least
One Endophenotype in Current
Study
DRD3a
rs2134655, rs963468, rs6280
DTNBP1a
rs1040410, rs760666, rs2619539,
rs3213207, rs1011313, rs2619528,
rs2619522, rs1018381, rs909706
ERBB4a
rs7598440
GABRB2a
rs187269, rs252944, rs194072,
rs1816072, rs1816071
GAD1a
rs2241165, rs3791850
GRID1a
rs2814351
GRIK3 rs3767045
GRIK4a
rs948028, rs2852217, rs879602,
rs1954787, rs4935752, rs6589846,
rs433110, rs7111184, rs2156635,
rs949054
rs948028
GRIN1a
rs11146020 rs11146020b
GRIN2Ba
rs1805502, rs890, rs1805247,
rs1806201, rs7301328
GRM3a
rs6465084, rs2237562, rs1468412
HTR2A rs7333412, rs2296972, rs659734,
rs6313
rs6313b
TABLE 1. Single-Nucleotide Polymorphisms (SNPs) in 33 Genes
Assayed in 130 Families and Associated With Schizophrenia or
Related Phenotypes in Previous Studies
72. Gene SNP Identifiers Associated (p<0.01) With at Least
One Endophenotype in Current
Study
HTR7a
rs12412496
NCAM1 rs1943620, rs1836796, rs1821693,
rs646558, rs2303377
NEUROG1a
rs2344485, rs2344484
NOTCH4a
rs422951, rs520692, rs915894
PPP1R1Ba
rs4795390, rs879606, rs907094,
rs3764352
RGS4a
rs2661319, rs2842030
SLC18A1 rs1390938, rs2270637, rs2270641,
rs17092104
rs17092104b
SLC6A3a
rs11564773, rs6876225, rs2550936,
rs6347, rs11564759, rs11564758,
rs2963238
rs11564773b
, rs11564758b
SP4 rs11974306, rs12668354,
rs12673091
rs12668354b
TAAR6a
rs8192625, rs4305745, rs6903874
ZDHHC8a
rs175174
TABLE 1. Single-Nucleotide Polymorphisms (SNPs) in 33 Genes
Assayed in 130 Families and Associated With Schizophrenia or
Related Phenotypes in Previous Studies
73. Is Schizophrenia Genetic?
• The only gene strongly connected to
schizophrenia is a gene on chromosome
22 named COMT. When abnormal, COMT
depletes the frontal lobes in the brain of
the neurochemical dopamine, causing
hallucinations and an impaired sense of
reality, both symptoms of schizophrenia.
• Not entirely: there are certain genes that
contribute, but onset depends on the environment
around the individual.
74. Can Schizophrenia Be Inherited?
• No, not specifically. There is one gene linked to
the disorder; however, little heredity is found in
schizophrenia.
• The highest instance of there being
two cases of schizophrenia in a family is
between twins, and the instance of that is
less than 50%, suggesting that
schizophrenia is not inherited. Again, it
depends on the environment around the
individual.
75. “If you talk to God,
you are praying;
if God talks to you,
you have schizophrenia”
76. “Human beings are ultimately
nothing but carriers-passageways-
for genes.
They ride us into the ground like
racehorses from generation to
generation. Genes don't think about
what constitutes good or evil.
They don't care whether we are happy or
unhappy. We're just means to an end for them.
The only thing they think about is what is
most efficient for them.”
Haruki Murakami, 1Q84
Editor's Notes
Relative risk for schizophrenia is around:
1% for normal population
5.6% for parents
10.1% for siblings
12.8% for children
50% in twins(especially identical @ monozygotic twins.)
Ideogram showing major chromosomal regions implicated by linkage studies of schizophrenia. Blue lines indicate areas for which suggestive evidence of linkage has been found in more than one data set. Red lines indicate regions where evidence of linkage has achieved genome-wide significance. Red arrows indicate the site of chromosomal abnormalities associated with schizophrenia. Yellow circles indicate the location of genes implicated as possible schizophrenia susceptibility loci.
a Other associated SNPs in these genes were not included because quality genotyping assays using this method were not available for these SNPs.
b Effect was in the same direction as in the previous studies