Non-drug treatments
1. Environmental Enrichment (EE): It has been indicated
alternations in neurotransmitters levels such as glutamate, serotonin,
and decreased BDNF induced by chronic isolation were modified in EE
(89). Social activity among rats exposed to a novel environment was
higher than standard rats. These results proved the potentiality of
nondrug protocols in improving mental deficits (97). Moreover,
well-being in isolated patients is related to the quality of social
support; consequently, any prescription to encourage being social and
connected has been considered by the practitioner (98). EE, as a
non-pharmacological treatment, has been applied in some investigation.
Data have suggested that EE has enhanced social and cognitive deficits
in isolated patients. Several researchers have exhibited the importance
of positive and hopeful experiences in life to recover the brain from
behavioral dysfunction (99).
Anti-depressant effects of EE have been demonstrated by investigations
according to SI in rats (100). It has been shown that depression-related
behavior and related abnormalities followed by long-term isolation,
could be treated by EE. It can also perform as effective as fluoxetine;
however, side effects associated with a pharmacological drug would not
happen with EE treatment. Isolation-induced decrease in 5-HT level has
been regulated through EE treatment, and the 5-HT level has increased in
the hippocampus and prefrontal cortex (64). Finally, some investigations
revealed that using an EE increases the rate of neurogenesis to maintain
proliferation of dentate gyrus (DG) hippocampal cells in socially
isolated mice, which results in maintaining social recognition memory
and improving amnesic-like impairment (101).
In conclusion, EE plays a significant role in promoting neurogenesis in
the hippocampus, impaired by social isolation.
2. Exercise: Frequent physical exercise has been accepted among
people to improve the physical and emotional conditions. By designing
several studies on sports achievements, it has demonstrated that
neurotransmitters’ functionality and brain plasticity have been
modulated in socially isolated rodents (102). In several types of
research, rats were forced to run on a treadmill, which was a
stressful condition. Results were disparate compared to voluntarily
exercise, which resulted in regulating BDNF levels in isolated rats.
Some other investigations have revealed that elective exercise cannot
make any improvements in cognitive and social behavior impairments (103,
104). Eight weeks of running on a treadmill (30 min/day) have been shown
to improve short-term and spatial working memory in SI rats (105).
Regular treadmill exercise has improved isolation-induced
depression-like behavior by regulating the
hypothalamic-pituitary-adrenal (HPA) axis and this type of exercise has
decreased stress hormones. Additionally, increased BDNF, NGF,
serotonergic cells, and brain plasticity in the hippocampus have
occurred after physical activity (22, 106).
Clinical research has revealed that walking among adults has
positively affected social experiences for people who have been isolated
and lived alone. At the end of this research, adults have claimed an
improvement in their feelings and are encouraged to start social
relationships, to get to know new people, and finally, to leave
isolating mood (107). As stated by the research on rats, it has
indicated that the development of monoaminergic axons has been prevented
during isolation periods in maternal separation (108).
Eventually, voluntarily running exercise has been found to stop
emotional and social impairments by stimulating monoaminergic axons to
start improvements again (109).
As claimed by more studies, pro-inflammatory and cytokine interleukin-1β
(IL-1β) has been produced increasingly in the hippocampus during the
adolescence period. Besides, Social isolation adversely affects the
hippocampus neurogenesis. Adolescence is a critical period in
hippocampus maturation, and any detrimental impact makes more impairment
in adulthood (110, 111). These Researches have found
that aerobic exercises decreased stress induced by both
adolescence and isolation in the hippocampus. Eventually, it has been
demonstrated by some evidence that overexpression of IL-1β has been
reversed by running and aerobic exercise during isolation housing in
adolescence; while, supportive effects on neurogenesis occurred at the
same time and resulted in developed recognition and social activity
(111, 112). These findings explained how SI changed 5-hydroxytryptamine
expression, and led to apoptosis in rats, which can account for
cognition deficit and anxiety mood. Investigations have also designed an
experiment to explore swimming effects on socially isolated old
rats (113).
Tryptophan hydroxylase positive cell, 5-hydroxytryptamine positive
cells, and Bcl-2 (B-cell lymphoma 2) expression have increased while BAX
(Bcl-2-associated X protein) and cytochrome c expression were
suppressed while swimming exercise. It was shown that swimming would
lead to apoptosis prevention, reduced anxiety, and enhancement in
social and learning capability in rats (114).
As claimed via an earlier investigation, depression was seen after
periods of SI, which impaired the glutamatergic system in the
hippocampus and NMDA receptor co-agonist D-serine. It has revealed
that endurance exercise has attenuated adverse effects induced
by isolation (115, 116). Amelioration of glutamate transmission has also
decreased depressive behavior in rats. Therefore, exercising has been
able to decline depression, social deficits, and cognition impairment
induced by isolation experiences (117).
3. Music: Music is well known as a way to express emotion and
has effects on well-being feeling, regulating hormones, and
neurotransmitters. Physicians have found music therapy as a
method to alleviate patients who had shown regression and weak
sociability during housing isolation (118). Two types of patients,
adults in the general ward of the hospital and children with leukemia in
an isolated room, have experienced it as an enjoyable practice (119).
They have claimed reduced fears, stress, and a motivated mood by
listening to music. Besides, more verbalization, self-expression, and
social relationships were reported. Beneficial impacts of listening to
music have been performed by neurochemicals such as dopamine and
oxytocin, which resulted in active talking and better communication
(120). It has also enhanced health conditions in patients with
Parkinson’s disease by increasing social benefit.
In conclusion, music has been considered a non-pharmacological treatment
in isolated patients and SI (121).
4. Technology: As mentioned earlier, the environment itself
plays a critical role in brain function and development. Lack of social
interaction, as an absence of social stimulation on the brain, may lead
to lesser cognitive reserve, lower brain flexibility, and cognitive
impairment (122). There are several investigations on
using smartphones, which have been used as a critical tool to
connect humans and plays a crucial role in social capability and
decreasing SI (123). Nowadays, social interaction has strictly wired
into mobile phones via social platforms such as chat rooms, groups and
channels, YouTube videos, and video-call applications like Skype. During
the pandemic, when getting quarantine and staying at home was advised,
social support has been provided mostly by social media throughout
smartphones. People could join in social activities and feel like a
helpful member of the community to reduce the detrimental effects of
isolation (124). Social engagement has shown to improve
age-related cognitive deficits, dementia, and memory decline induced by
SI. Moreover, a sense of belonging and connection with others in places
like school has shown to be crucial for academic success (125).
During the COVID-19 pandemic, Attitudes towards social
robots have changed. Pieces of evidence have shown that people were
encouraged to buy social robots more than ever. The emotional and
behavioral features of those robots have made people feel less lonely
and isolated; also, social support and reduced depressive-like mood were
reported. A sense of happiness and having a better quality of life was
seen through interactions with a robot, which was designed to behave
socially interactive (126-128).
5. Farming: Farming activities have been shown to regulate
social functioning for those who are suffering from a mental disorder.
Several investigations have revealed that farming activities moderated
getting into the community and having a connection with people. Being
with each other is essential for people with mental problems; therefore,
drug treatments will not work when social bonds are weak. According to
the current research, social farming has been useful for social
interaction and fihjting isolation (129, 130).