MK4MDD

Hot Components

Genetic/epigenetic locus   Protein and other molecule   Cell and molecular pathway   Neural system   Cognition and behavior   Symptoms and signs   Environment
SNP Gene Protein Molecule Pathway Cell Neurobiological system Brain morphology and function Cognition and behavior Symptoms Signs Environment
Hot SNPs (No. of studies >= 2) (count: 32)
#rs Location Variant Alleles Annotation No. of Studies (Positive/Negative)
rs6265 chr11:27658369(Forward) C/T 9(5/4)
rs1006737 chr12:2236129(Forward) G/A 7(6/1)
rs2230912 chr12:121184393(Forward) A/G 6(3/3)
rs4680 chr22:19963748(Forward) G/A 4(2/2)
rs2522833 chr7:82824392(Forward) A/C 4(4/0)
rs1137070 chrX:43744144(Forward) T/C 3(3/0)
rs242939 chrCHR_HSCHR17_2_CTG5:45829832(Forward) T/C 3(3/0)
rs2535629 chr3:52799203(Forward) G/A regulatory_region_variant 3(1/2)
rs11030101 chr11:27659197(Forward) A/T 3(1/2)
rs9340799 chr6:151842246(Forward) A/G 3(3/0)
rs1360780 chr6:35639794(Forward) T/C 3(2/1)
rs2242446 chr16:55656513(Forward) C/T regulatory_region_variant 2(2/0)
rs2287161 chr12:106987362(Forward) C/G regulatory_region_variant 2(2/0)
rs6313 chr13:46895805(Forward) G/A 2(1/1)
rs9939609 chr16:53786615(Forward) T/A 2(1/1)
rs28722151 chr11:27659629(Forward) C/G 2(1/1)
rs2072446 chr17:49510457(Forward) C/T 2(2/0)
rs1801133 chr1:11796321(Forward) G/A 2(1/1)
rs766288 chr1:231557942(Forward) G/T regulatory_region_variant 2(2/0)
rs4478239 chr4:187270152(Forward) C/A 2(0/2)
rs619002 chr2:31266099(Forward) C/T 2(2/0)
rs1545843 chr12:84170289(Forward) G/A 2(2/0)
rs110402 chrCHR_HSCHR17_2_CTG5:45814295(Forward) G/A 2(2/0)
rs821616 chr1:232008852(Forward) A/T 2(1/1)
rs6198 chr5:143278056(Forward) T/C 2(2/0)
rs6311 chr13:46897343(Forward) C/T 2(1/1)
rs2234693 chr6:151842200(Forward) T/C 2(2/0)
rs1539243 chr1:206474444(Forward) T/C 2(1/1)
rs3738401 chr1:231694549(Forward) G/A 2(2/0)
rs2715148 chr7:82820719(Forward) A/C 2(2/0)
rs40184 chrCHR_HSCHR5_3_CTG1:1437345(Reverse) T/C 2(1/1)
rs644926 chr2:31266861(Forward) T/C 2(2/0)

Hot genes (No. of studies >= 5) (count: 22)
Approved Symbol Approved Name Location Type No. of Studies (Positive/Negative)
SLC6A4 solute carrier family 6 (neurotransmitter transporter), member 4 17q11.2 Literature-origin; Protein mapped 56(44/12)
BDNF brain-derived neurotrophic factor 11p14.1 Literature-origin; SNP mapped; Protein mapped 28(19/9)
TPH2 tryptophan hydroxylase 2 12q15 Literature-origin; SNP mapped; Protein mapped 15(11/4)
HTR1A 5-hydroxytryptamine (serotonin) receptor 1A, G protein-coupled 5q11.2-q13 Literature-origin; Protein mapped 15(11/4)
MAOA monoamine oxidase A Xp11.4-p11.3 Literature-origin; SNP mapped; Protein mapped 13(9/4)
TPH1 tryptophan hydroxylase 1 11p15.3-p14 Literature-origin 13(9/4)
CREB1 cAMP responsive element binding protein 1 2q34 Literature-origin; Protein mapped 12(10/2)
COMT catechol-O-methyltransferase 22q11.21 Literature-origin; SNP mapped 11(8/3)
HTR2A 5-hydroxytryptamine (serotonin) receptor 2A, G protein-coupled 13q14-q21 Literature-origin; SNP mapped; Protein mapped 11(7/4)
NR3C1 nuclear receptor subfamily 3, group C, member 1 (glucocorticoid receptor) 5q31-q32 Literature-origin; Protein mapped 8(8/0)
GSK3B glycogen synthase kinase 3 beta 3q13.3 Literature-origin; Protein mapped 7(6/1)
CRHR1 corticotropin releasing hormone receptor 1 17q12-q22 Literature-origin; SNP mapped; Protein mapped 7(6/1)
ACE angiotensin I converting enzyme 17q23.3 Literature-origin; SNP mapped; Protein mapped 7(6/1)
ELK3 ELK3, ETS-domain protein (SRF accessory protein 2) 12q23 Literature-origin 7(5/2)
TNF tumor necrosis factor 6p21.3 Literature-origin; SNP mapped; Protein mapped 7(7/0)
NPY neuropeptide Y 7p15.3 Literature-origin; SNP mapped; Protein mapped 7(6/1)
SLC1A2 solute carrier family 1 (glial high affinity glutamate transporter), member 2 11p13-p12 Literature-origin; Protein mapped 6(3/3)
NTRK2 neurotrophic tyrosine kinase, receptor, type 2 9q22.1 Literature-origin; Protein mapped 6(5/1)
P2RX7 purinergic receptor P2X, ligand-gated ion channel, 7 12q24 Literature-origin; SNP mapped 6(5/1)
HTR1B 5-hydroxytryptamine (serotonin) receptor 1B, G protein-coupled 6q13 Literature-origin; Protein mapped 5(4/1)
DRD2 dopamine receptor D2 11q22-q23 Literature-origin; Protein mapped 5(3/2)
MTHFR methylenetetrahydrofolate reductase (NAD(P)H) 1p36.3 Literature-origin; SNP mapped 5(1/4)

Hot proteins (No. of studies >= 5) (count: 20)

Hot molecules (No. of studies >= 5) (count: 13)
Name MeSH ID No. of Studies (Positive/Negative)
Hydrocortisone D006854 68(67/1)
Glutamates D005971 19(19/0)
Tryptophan D014364 13(13/0)
Serotonin D012701 12(12/0)
Choline D002794 11(10/1)
gamma-Aminobutyric Acid D005680 11(11/0)
Creatine D003401 10(9/1)
Glutamine D005973 10(10/0)
Inositol D007294 10(9/1)
N-acetylaspartate C000179 10(9/1)
Dopamine D004298 8(8/0)
Cholesterol D002784 6(6/0)
Nitric oxide D009569 6(6/0)

Hot pathways (No. of studies >= 2) (count: 10)

Hot cells (No. of studies >= 3) (count: 7)
Name System CCDB ID No. of Studies (Positive/Negative)
Killer Cells, Natural immune system. 16(15/1)
Neuroglia nervous system 7(7/0)
Lymphocytes 6(6/0)
pyramidal neuron centra nervous system 51 6(6/0)
Leukocytes 5(5/0)
Blood Platelets 3(3/0)
Astrocytes 3(2/1)

Hot neurobiological components (No. of studies >= 5) (count: 14)
Name No. of Studies (Positive/Negative) Picture
P300 18(17/1)
Hypothalamic-pituitary-adrenal axis 17(17/0)
Alpha wave 15(15/0)
Rapid eye movement (REM) sleep 12(12/0)
Serotonergic system 11(11/0)
Delta wave 9(9/0)
P200 9(9/0)
Late positive component 9(9/0)
N200 8(8/0)
Error-related negativity (ERN) 8(8/0)
Theta wave 7(7/0)
P100 6(6/0)
N400 5(5/0)
Electroencephalographic activity 5(5/0)

Hot brain morphology and function components (No. of studies >= 15) (count: 17)
Name No. of Studies (Positive/Negative) Picture
Hippocampus 93(90/3)
Amygdala 89(87/2)
Anterior cingulate cortex 72(71/1)
White matter 42(42/0)
Orbitofrontal cortex 34(34/0)
Dorsolateral prefrontal cortex 32(32/0)
Prefrontal cortex 31(30/1)
Caudate nucleus 29(29/0)
Thalamus 23(23/0)
Cerebellum 22(22/0)
Insula 20(20/0)
Attention network 19(19/0)
Temporal Lobe 18(18/0)
Posterior cingulate cortex 17(17/0)
Putamen 17(17/0)
Frontal Lobe 16(15/1)
Left amygdala 15(15/0)

Hot cognition and behavior components (No. of studies >= 5) (count: 20)
Name No. of Studies (Positive/Negative) Description
Memory 31(31/0) "In psychology, memory is an organism's ability to store, re...... "In psychology, memory is an organism's ability to store, retain, and recall information and experiences. " More...
Attention 29(29/0) Attention is the cognitive process of selectively concentrat...... Attention is the cognitive process of selectively concentrating on one aspect of the environment while ignoring other things. Attention has also been referred to as the allocation of processing resources. More...
Executive functions 28(28/0) "The executive system is a theorized cognitive system in psy...... "The executive system is a theorized cognitive system in psychology that controls and manages other cognitive processes. It is responsible for processes that are sometimes referred to as the executive function, executive functions, supervisory attentional system, or cognitive control. However, executive function and cognitive control are not synonymous with an executive system with the former potentially carried out by specific brain areas or networks (e.g., anterior cingulate cortex and prefrontal cortex in attention, cf. Botvinick et al., 2001; see also Verguts & Notebaert, 2009). The concept is used by psychologists and neuroscientists to describe a loosely defined collection of brain processes that are responsible for planning, cognitive flexibility, abstract thinking, rule acquisition, initiating appropriate actions and inhibiting inappropriate actions, and selecting relevant sensory information." More...
Cognitive processing bias 28(28/0) "A cognitive bias is a pattern of deviation in judgment that...... "A cognitive bias is a pattern of deviation in judgment that occurs in particular situations. Implicit in the concept of a ""pattern of deviation"" is a standard of comparison; this may be the judgment of people outside those particular situations, or may be a set of independently verifiable facts. Cognitive biases are instances of evolved mental behavior. Some are presumably adaptive, for example, because they lead to more effective actions in given contexts or enable faster decisions when faster decisions are of greater value. Others presumably result from a lack of appropriate mental mechanisms, or from the misapplication of a mechanism that is adaptive under different circumstances. Cognitive bias is a general term that is used to describe many observer effects in the human mind, some of which can lead to perceptual distortion, inaccurate judgment, or illogical interpretation." More...
Cognitive performance 19(18/1)
Emotion 19(19/0) "Emotion is the complex psychophysiological experience of an...... "Emotion is the complex psychophysiological experience of an individual's state of mind as interacting with biochemical (internal) and environmental (external) influences. In humans, emotion fundamentally involves ""physiological arousal, expressive behaviors, and conscious experience.""" More...
Reaction time 18(17/1) "Mental chronometry is the use of response time in perceptua...... "Mental chronometry is the use of response time in perceptual-motor tasks to infer the content, duration, and temporal sequencing of cognitive operations. Mental chronometry is studied using the measurements of reaction time (RT). Reaction time is the elapsed time between the presentation of a sensory stimulus and the subsequent behavioral response. In psychometric psychology it is considered to be an index of speed of processing. That is, it indicates how fast the thinker can execute the mental operations needed by the task at hand. In turn, speed of processing is considered an index of processing efficiency. The behavioral response is typically a button press but can also be an eye movement, a vocal response, or some other observable behavior." More...
Cognitive control 17(16/1) The cognitive control system is a theorized cognitive system...... The cognitive control system is a theorized cognitive system in psychology that controls and manages other cognitive processes. More...
Working memory 16(16/0) "Working memory has been defined as the system which activel...... "Working memory has been defined as the system which actively holds information in the mind to do verbal and nonverbal tasks such as reasoning and comprehension, and to make it available for further information processing. Working memory tasks are those that require the goal-oriented active monitoring or manipulation of information or behaviors in the face of interfering processes and distractions." More...
anhedonic-like behavior from animal model 16(15/1)
Reward processing 13(13/0) "A psychological reward is a process that reinforces behavio...... "A psychological reward is a process that reinforces behavior - something that, when offered, causes a behavior to increase in intensity. Reward is an operational concept for describing the positive value an individual ascribes to an object, behavioral act or an internal physical state. Natural rewards include those that are necessary for the survival of species, such as eating, drinking, sex, and fighting. Secondary rewards derive their value from the primary reward, and include shelter, money, pleasant touch, beauty, music, etc. The functions of rewards are based directly on the modification of behavior and indirectly on the sensory properties of rewards. For instance, altruism may induce a larger psychological reward, although it doesn't cause sensations. Rewards are generally considered more effective than punishment in enforcing positive behavior. Rewards induce learning, approach behavior and feelings of positive emotions." More...
Depression-like behaviors from animal model 12(12/0) Depression-like behaviors from animal model. Depression-like behaviors from animal model.
Sensation 9(8/1) "Sensation is the process of receiving, converting, and tran...... "Sensation is the process of receiving, converting, and transmitting raw sensory information from the external and internal environment to our brain. Sensation is the function of the low-level biochemical and neurological events that begin with the impinging of a stimulus upon the receptor cells of a sensory organ. In psychology, sensation and perception are stages of processing of the senses in human and animal systems, such as vision, auditory, vestibular, and pain senses." More...
Learning 9(9/0) "Learning is acquiring new or modifying existing knowledge, ...... "Learning is acquiring new or modifying existing knowledge, behaviors, skills, values, or preferences and may involve synthesizing different types of information. " More...
Language 7(7/0) "Language may refer either to the specifically human capacit...... "Language may refer either to the specifically human capacity for acquiring and using complex systems of communication, or to a specific instance of such a system of complex communication. " More...
Verbal memory 7(7/0) Verbal memory is a term used in cognitive psychology that re...... Verbal memory is a term used in cognitive psychology that refers to memory of words and other abstractions involving language. More...
Attribution and attitude 6(5/1) "Attribution is a concept in social psychology referring to ...... "Attribution is a concept in social psychology referring to how individuals explain causes of behavior and events. An attitude is a hypothetical construct that represents an individual's degree of like or dislike for something. Attitudes are generally positive or negative views of a person, place, thing, or event- this is often referred to as the attitude object. People can also be conflicted or ambivalent toward an object, meaning that they simultaneously possess both positive and negative attitudes toward the item in question. " More...
Accuracy for reaction 6(5/1)
Anxiety-like behaviors from animal model 6(5/1) Anxiety-like behaviors from animal model. Anxiety-like behaviors from animal model.
Perception 5(5/0) "Perception is the process of attaining awareness or underst...... "Perception is the process of attaining awareness or understanding of the environment by organizing and interpreting sensory information. All perception involves signals in the nervous system, which in turn result from physical stimulation of the sense organs. Perception is not the passive receipt of these signals, but can be shaped by learning, memory and expectation. Perception involves these ""top-down"" effects as well as the ""bottom-up"" process of processing sensory input." More...

Hot symptoms (No. of studies >= 5) (count: 13)
Name No. of Studies (Positive/Negative) Description
Depressed mood 117(111/6) "Depression is a state of low mood and aversion to activity ...... "Depression is a state of low mood and aversion to activity that can affect a person's thoughts, behavior, feelings and physical well-being. It may include feelings of sadness, anxiety, emptiness, hopelessness, worthlessness, guilt, irritability, or restlessness." More...
Suicide 88(81/7) "Suicide is the act of a human being intentionally causing h...... "Suicide is the act of a human being intentionally causing his or her own death. Suicide is often committed out of despair, or attributed to some underlying mental disorder which includes depression, bipolar disorder, schizophrenia. The rate of suicide is higher in men than in women. There are an estimated 10 to 20 million non-fatal attempted suicides every year worldwide." More...
Increased agitation 35(35/0) "Psychomotor agitation is a series of unintentional and purp...... "Psychomotor agitation is a series of unintentional and purposeless motions that stem from mental tension and anxiety of an individual. This includes pacing around a room, wringing one's hands, pulling off clothing and putting it back on and other similar actions. In more severe cases, the motions may become harmful to the individual, such as ripping, tearing or chewing at the skin around one's fingernails or lips to the point of bleeding. Psychomotor agitation is a symptom typically found in major depressive disorder or obsessive-compulsive disorder, and sometimes the manic phase in bipolar disorder, although it can also be a result of an excess intake of stimulants. The middle aged and the elderly are more at risk to express this condition." More...
Anhedonia 34(34/0) "In psychology and psychiatry, anhedonia is defined as the i...... "In psychology and psychiatry, anhedonia is defined as the inability to experience pleasure from activities formerly found enjoyable, e.g. hobbies, exercise, social interaction or sexual activity. As a clinical symptom in depression, anhedonia rates highly in making a diagnosis of this disorder. The Diagnostic and Statistical Manual of Mental Disorders (DSM) describes a ""lack of interest or pleasure"" but these can be hard to tell apart given that people become less interested in things which do not give them pleasure. The DSM criterion of weight loss is probably related to it and many depressed people with this symptom describe a lack of enjoyment of food. People suffering from anhedonia in association with depression generally feel good in the morning and unhappy in the evenings and can portray any of the non-psychotic symptoms and signs of depression." More...
Sleep disturbances 32(32/0) "Sleep disturbances mainly include insomnia and hypersomnia...... "Sleep disturbances mainly include insomnia and hypersomnia. Insomnia is most often defined by an individual's report of sleeping difficulties. Insomnia is typically followed by functional impairment while awake. One definition of insomnia is difficulties initiating and/or maintaining sleep, or nonrestorative sleep, associated with impairments of daytime functioning or marked distress for more than 1 month. Hypersomnia is a disorder characterized by excessive amounts of sleepiness. Hypersomnia can be caused by brain damage and disorders such as clinical depression. Insomnia affects at least 80% of depressed people. Hypersomnia, or oversleeping, can also happen, affecting 15% of depressed people." More...
Low energy 26(26/0) "Psychomotor retardation or psychomotor impairment comprises...... "Psychomotor retardation or psychomotor impairment comprises a slowing down of thought and a reduction of physical movements in an individual. Psychomotor Retardation can cause a visible slowing of physical and emotional reactions including speech and affect. This is most commonly seen in people with major depression, as well as in the depressed phase of bipolar disorder." More...
Irritability 21(21/0) "Irritability is an excessive response to stimuli. The term ...... "Irritability is an excessive response to stimuli. The term is used for both the physiological reaction to stimuli and for the pathological, abnormal or excessive sensitivity to stimuli; It is usually used to refer to anger or frustration. Irritability may be demonstrated in behavioral responses to both physiological and behavioral stimuli including environmental, situational, sociological, and emotional stimuli." More...
Psychotic symptoms 19(19/0) "In severe cases, depressed people may have symptoms of psyc...... "In severe cases, depressed people may have symptoms of psychosis. These symptoms include delusions or, less commonly, hallucinations, usually unpleasant." More...
"Feelings of hopelessness, worthlessness, and guilt" 8(8/0) "Depressed people may be preoccupied with, or ruminate over,...... "Depressed people may be preoccupied with, or ruminate over, thoughts and feelings of worthlessness, inappropriate guilt or regret, helplessness, hopelessness, and self-hatred." More...
Fatigue 7(7/0) "Fatigue is a state of awareness describing a range of affli...... "Fatigue is a state of awareness describing a range of afflictions, usually associated with physical and/or mental weakness, though varying from a general state of lethargy to a specific work-induced burning sensation within one's muscles." More...
Decreased appetite 6(6/0) "A depressed person may report multiple physical symptoms. A...... "A depressed person may report multiple physical symptoms. Appetite often decreases, with resulting weight loss, although increased appetite and weight gain occasionally occur." More...
Somatic symptoms 5(5/0) "Somatic symptoms are common in patients with MDD, including...... "Somatic symptoms are common in patients with MDD, including fatigue and lack of energy and painful physical symptoms such as headaches and back pain. According to an analysis of data from the World Health Organization, 69% of patients in primary care settings meeting the DSM-IV/ICD-10 criteria for depression presented somatic symptoms as their primary reason for seeking medical care. Somatic symptoms in depressed patients, in particular painful physical symptoms, are associated with more severe depression of longer duration and greater functional impairment, poorer clinical outcome and higher health-care costs. Furthermore, the overlap of somatic symptoms associated with depression with other medical illnesses can impact accurate diagnosis and lead to the under-recognition of depression and misdiagnosis (Vaccarino et al, 2008; PMID: 18280580)." More...
hopelessness 5(5/0) Depression is a state of low mood and aversion to activity t...... Depression is a state of low mood and aversion to activity that can affect a person's thoughts, behavior, feelings and sense of well-being. People with a depressed mood can feel sad, anxious, empty, hopeless, helpless, worthless, guilty, irritable, ashamed or restless. More...

Hot signs (No. of studies >= 5) (count: 5)
Name No. of Studies (Positive/Negative) Description
Blood pressure (BP) 8(8/0) "Blood pressure (BP) is the pressure exerted by circulating ...... "Blood pressure (BP) is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. During each heartbeat, BP varies between a maximum (systolic) and a minimum (diastolic) pressure." More...
Heart rate (HR) 7(7/0) "Heart rate is the number of heartbeats per unit of time, ty...... "Heart rate is the number of heartbeats per unit of time, typically expressed as beats per minute (bpm). Heart rate can vary as the body's need to absorb oxygen and excrete carbon dioxide changes, such as during exercise or sleep." More...
Cortisol awakening response 3(3/0) The cortisol awakening response (CAR) is an increase of abou...... The cortisol awakening response (CAR) is an increase of about 50% in cortisol levels occurring 20-30 minutes after awakening in the morning in some people. This rise is superimposed upon the late-night rise in cortisol which occurs before awakening. It is thought to be linked to the hippocampus' preparation of the hypothalamic-pituitary-adrenal axis (HPA) to face anticipated stress. More...
QT interval 2(2/0) "In cardiology, the QT interval is a measure of the time bet...... "In cardiology, the QT interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle. In general, the QT interval represents electrical depolarization and repolarization of the left and right ventricles. A prolonged QT interval is a biomarker for ventricular tachyarrhythmias like torsades de pointes and a risk factor for sudden death." More...
Baroreflex 2(2/0) "The baroreflex or baroreceptor reflex is one of the body's ...... "The baroreflex or baroreceptor reflex is one of the body's homeostatic mechanisms for maintaining blood pressure. It provides a negative feedback loop in which an elevated blood pressure reflexively causes heart rate and, thus, blood pressure to decrease; in similar fashion, decreased blood pressure activates the baroreflex, causing heart rate and, thus, blood pressure to rise." More...

Hot environments (No. of studies >= 5) (count: 4)
Name No. of Studies (Positive/Negative) Description
Stress 31(39/1) "The diathesis-stress model specifies that depression result...... "The diathesis-stress model specifies that depression results when a preexisting vulnerability, or diathesis, is activated by stressful life events. In adulthood, stressful life events are strongly associated with the onset of major depressive episodes." More...
Child abuse 20(22/0) "Child abuse is the physical, sexual, emotional mistreatment...... "Child abuse is the physical, sexual, emotional mistreatment, or neglect of children. Child abuse can occur in a child's home, or in the organizations, schools or communities the child interacts with. There are four major categories of child abuse: neglect, physical abuse, psychological/emotional abuse, and child sexual abuse. Child abuse (physical, emotional, sexual, or neglect) is also associated with increased risk of developing depressive disorders later in life. Such a link has good face validity given that it is during the years of development that a child is learning how to become a social being. Abuse of the child by the caregiver is bound to distort the developing personality and create a much greater risk for depression and many other debilitating mental and emotional states." More...
Life events 9(9/0)
Physical exercise 5(6/0)