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1.

Schizophrenia

Schizophrenia is highly heritable, as shown by family, twin, and adoption studies. For example, for identical twins, if one twin develops schizophrenia, the other twin has about a 50% chance of also developing the disease. The risk of the general population developing the schizophrenia is about 0.3-0.7% worldwide. The search for “schizophrenia genes” has been elusive. Initial linkage studies looked at parts of the genome associated with schizophrenia, and many candidate genes were identified, including APOE, COMT, DAO, DRD1, DRD2, DRD4, DTNBP1, GABRB2, GRIN2B, HP, IL1B, MTHFR, PLXNA2, SLC6A4, TP53, and TPH1. However, some of these have later been questioned. Microdeletions and microduplications have been found to be three times more common in individuals with schizophrenia, compared to controls. Because these deletions and duplications are in genes that are overexpressed in pathways related to brain development, it is possible that the inheritance of multiple rare variants may contribute to the development of schizophrenia. Several genetic disorders feature schizophrenia as a clinical feature. The 22q11.2 Deletion Syndrome comprises many different syndromes, of which one of the most serious is DiGeorge syndrome. Children born with DiGeorge syndrome typically have heart defects, cleft palate, learning difficulties, and immune deficiency. Schizophrenia is a late manifestation, affecting around 30% of individuals. Microdeletions and duplications in chromosome 1, 2, 3, 7, 15 and 16 have also been associated with schizophrenia. In 2014, a genome-wide association study looked at the genomes of over 35,000 patients and 110,00 controls. The study identified 108 SNPs that were associated with schizophrenia, 83 of which had not been previously reported. As expected, many of these loci occurred in genes that are expressed in the brain. For example, the SNPs included a gene that encodes the dopamine D2 receptor, DRD2 (the target of antipsychotic drugs), and many genes involved in glutamine neurotransmitter pathways and synaptic plasticity (e.g., GRM3, GRIN2A, SRR, GRIA1). More surprisingly, however, associations were also enriched among genes expressed in tissues with important immune functions. In 2016, a study based on nearly 65,000 people investigated the association between schizophrenia and variation in the Major Histocompatibility Complex (MHC) locus—a region on chromosome 6 that is important for immune function. The study focused on the C4 gene (complement component 4) that exists as two distinct genes: C4A and C4B, which encode particularly structurally diverse alleles. The study found that the alleles which promoted greater expression of C4A in the brain were associated with a greater risk of schizophrenia. By using mice models, the study showed that C4 is involved in the elimination of synapses during brain maturation. In humans, “synaptic pruning” is most active during late adolescence, which coincides with the typical onset of symptoms of schizophrenia. It is therefore possible that the inheritance of specific C4A alleles could lead to “run away” synaptic pruning, increasing the risk of schizophrenia. Further research may even determine C4 as a potential therapeutic target. [from Medical Genetics Summaries]

MedGen UID:
48574
Concept ID:
C0036341
Mental or Behavioral Dysfunction
2.

Schizophrenia

A mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social or occupational dysfunction. The onset of symptoms typically occurs in young adulthood, with a global lifetime prevalence of about 0.3-0.7%. [from HPO]

MedGen UID:
506532
Concept ID:
CN117643
Finding
3.

Mental Depression

Depression is a serious medical illness that involves the brain. It's more than just a feeling of being "down in the dumps" or "blue" for a few days. If you are one of the more than 20 million people in the United States who have depression, the feelings do not go away. They persist and interfere with your everyday life. Symptoms can include . -Sadness. -Loss of interest or pleasure in activities you used to enjoy. -Change in weight. -Difficulty sleeping or oversleeping. -Energy loss. -Feelings of worthlessness. -Thoughts of death or suicide. Depression is a disorder of the brain. There are a variety of causes, including genetic, environmental, psychological, and biochemical factors. Depression usually starts between the ages of 15 and 30, and is much more common in women. Women can also get postpartum depression after the birth of a baby. Some people get seasonal affective disorder in the winter. Depression is one part of bipolar disorder. There are effective treatments for depression, including antidepressants and talk therapy. Most people do best by using both. . NIH: National Institute of Mental Health.  [from MedlinePlus]

MedGen UID:
8325
Concept ID:
C0011570
Mental or Behavioral Dysfunction
4.

Anxiety

Fear and anxiety are part of life. You may feel anxious before you take a test or walk down a dark street. This kind of anxiety is useful - it can make you more alert or careful. It usually ends soon after you are out of the situation that caused it. But for millions of people in the United States, the anxiety does not go away, and gets worse over time. They may have chest pains or nightmares. They may even be afraid to leave home. These people have anxiety disorders. Types include. -Panic disorder . -Obsessive-compulsive disorder . -Post-traumatic stress disorder . -Phobias . -Generalized anxiety disorder . Treatment can involve medicines, therapy or both. NIH: National Institute of Mental Health .  [from MedlinePlus]

MedGen UID:
1613
Concept ID:
C0003467
Finding; Finding
5.

Depression

MedGen UID:
881016
Concept ID:
CN236657
Disease or Syndrome
6.

Anxiety

Human personality is shaped by genetic and environmental factors, and evidence suggests that the genetic component is highly complex, polygenic, and epistatic. Genetic factors are thought to contribute to 40 to 60% of trait variance. Molecular genetics has tried to identify specific genes for quantitative traits, called quantitative trait loci (QTLs). The QTL concept suggests that complex personality traits or dimensions are not attributable to single genes, but to multiple interacting genes (Reif and Lesch, 2003). Fullerton et al. (2003) stated that psychologists were in agreement that the wide variation in human personalities can be explained by a small number of personality factors, including neuroticism (a measure of emotional stability), which manifests at one extreme as anxiety, depression, moodiness, low self-esteem, and diffidence. They cited a number of studies that had described a relationship between high scores on measures of neuroticism and major depressive disorder. They also noted that theoretical studies had suggested that large samples of randomly ascertained sibs could be used to ascertain phenotypically extreme individuals and thereby increase power to detect genetic linkage in complex traits. See also panic disorder (PAND1; 167870), which is a subtype of anxiety disorder. [from OMIM]

MedGen UID:
335849
Concept ID:
C1842981
Mental or Behavioral Dysfunction
7.

Depression

A condition characterized by pervasive dysphoric mood, loss of interests, and inability to experience pleasure. [from HPO]

MedGen UID:
4229
Concept ID:
C0011581
Mental or Behavioral Dysfunction
8.

Neurocognitive disorder

A disorder characterized by a decline primarily in intellectual function due to disease of the brain caused by a variety of acquired conditions such as cerebrovascular disease, Alzheimer's disease, infections, adverse drug reactions and trauma. [from SNOMEDCT_US]

MedGen UID:
873945
Concept ID:
C4041080
Mental or Behavioral Dysfunction
9.

Hypervigilance

Condition of elevated sensory sensitivity, perception of risk of threats, and low threshhold for stimuli. [from MeSH]

MedGen UID:
452297
Concept ID:
C0235013
Mental or Behavioral Dysfunction
10.

Schizophrenia and Disorders with Psychotic Features

Marked disorders of thought (delusions, hallucinations, or other thought disorder accompanied by disordered affect or behavior), and deterioration from a previous level of functioning. [from MeSH]

MedGen UID:
141907
Concept ID:
C0525046
Mental or Behavioral Dysfunction
11.

Diagnosis, Psychiatric

MedGen UID:
138165
Concept ID:
C0376338
Mental or Behavioral Dysfunction
12.

Personality disorder

Personality disorders are a group of mental illnesses. They involve long-term patterns of thoughts and behaviors that are unhealthy and inflexible. The behaviors cause serious problems with relationships and work. People with personality disorders have trouble dealing with everyday stresses and problems. They often have stormy relationships with other people. The cause of personality disorders is unknown. However, genes and childhood experiences may play a role. The symptoms of each personality disorder are different. They can mild or severe. People with personality disorders may have trouble realizing that they have a problem. To them, their thoughts are normal, and they often blame others for their problems. They may try to get help because of their problems with relationships and work. Treatment usually includes talk therapy and sometimes medicine.  [from MedlinePlus]

MedGen UID:
45827
Concept ID:
C0031212
Mental or Behavioral Dysfunction
13.

Latent schizophrenia

MedGen UID:
44075
Concept ID:
C0023105
Mental or Behavioral Dysfunction
14.

Cognitive disorder

disturbances in the mental process related to thinking, reasoning, and judgment. [from CRISP]

MedGen UID:
40371
Concept ID:
C0009241
Mental or Behavioral Dysfunction
15.

Schizotypal personality disorder

A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [from MeSH]

MedGen UID:
20666
Concept ID:
C0036363
Mental or Behavioral Dysfunction
16.

Borderline schizophrenia

MedGen UID:
20663
Concept ID:
C0036343
Mental or Behavioral Dysfunction
17.

Psychoses, Traumatic

MedGen UID:
19557
Concept ID:
C0033943
Mental or Behavioral Dysfunction
18.

Schizophrenia, Pseudoneurotic

MedGen UID:
19540
Concept ID:
C0033823
Mental or Behavioral Dysfunction
19.

Nervousness

An uneasy psychological state; the anxious feeling you have when you have the jitters. [from NCI]

MedGen UID:
18004
Concept ID:
C0027769
Finding; Sign or Symptom
20.

Overinclusion

MedGen UID:
14542
Concept ID:
C0029947
Mental or Behavioral Dysfunction
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