14

Bioinformatics of the Brain

results. This is the earliest pathological change in HD. This defect in cell

metabolism causes cell death in the striatum and a decrease in metabolic

enzymes for energy production in the brain [80]. The HD gene is located on

the short arm of chromosome 4 [81]. The mutation in exon 1 of this gene

causes an increase in the repeats of CAG trinucleotides. While there are less

than 35 CAG repeats in healthy individuals, this number increases to 37 and

above in individuals with HD. Increased CAG trinucleotide repeats result

in the addition of abnormally long polyglutamine sequences to the mutant

huntingtin (HTT) protein [82]. This is an indication that the gene defect

does not eliminate an essential gene, rather the enzyme activity decreases or

completely disappears due to repeat copy number changes in HD [82].

In HD, cognitive symptoms occur due to the weakening of selective cogni-

tive abilities. Accordingly, executive functions (planning, cognitive flexibility),

psychomotor functions (slowing down in intellectual processes related to mus-

cle control), perceptual and environmental abilities, choosing the right method

in remembering information and choosing new disorders in learning skills show

parallelism with the pathology in the individual [83]. In addition to various

physical and cognitive symptoms, the disease also includes psychiatric symp-

toms such as depression, anxiety, decreased emotional expression (emotional

limitation), and compulsive behaviors. Performance at work or in daily life

also declines in patients suffering from HD, and they must continue taking

medicine to maintain their quality of life [84]. In 80% of patients, psychiatric

symptoms rather than cognitive symptoms occur within the first 10–15 years

of the disease. The risk of suicide in HD patients is higher than in the general

population [85]. Furthermore, aggression and irritability have been reported to

be higher among Huntingtin gene carriers compared to the general population.

In contrast, obsessive-compulsive disorder (OCD), schizophrenia, and delu-

sional disorders can be observed less frequently in Huntington’s patients [86].

There is currently no treatment option to reverse or stop the degenera-

tive process in HD, but the treatment of HD is based on the symptoms [87].

Dopamine receptor blockers, benzodiazepines, drugs that empty dopamine

stores, and valproate can be used for the treatment of chorea. Drugs that re-

duce dopaminergic neurotransmission should be used with extreme caution,

as they may increase parkinsonism in advanced stages of the disease and in

juvenile-onset patients. Serotonin reuptake inhibitors can be used for depres-

sive symptoms [88]. While genetic testing is the gold standard for making the

final diagnosis of HD, neuroimaging tests can also provide valuable guidance.

Although striatal volume loss and increased volume in the frontal horn of

the lateral ventricles are findings supporting HD in structural brain imaging

studies, it should be underlined that these findings may not be detected in the

early stages of the disease. However, with functional neuroimaging techniques,

brain dysfunctions in, for example, lateral prefrontal and cingulate regions can

be demonstrated before the symptoms begin [89].

Even though the clinical diagnosis of HD is based on the presence of

the aforementioned motor symptoms, cognitive dysfunctions and psychiatric