Dissociative Disorders can result in significant changes in identity, cognition, personality, behavior, and physical health, as well as immune dysfunction. Findings indicate the core phenomenon of Depersonalization is associated with reduced neural responses in emotion-sensitive regions, and increased responses in regions associated with emotion regulation.  That is to say there is an over-regulation, or hypo-arousal, of emotional brain regions in the face of emotional stimuli, i.e. something that evokes an emotional response.
Colloquially, DPDR is often called The Lonely Disorder. Limbic regions play an important role in our emotional personalities. This under-activity may play a part in the social withdrawal, difficulty maintaining intimate relationships, feelings of emptiness, and lack of emotional control that accompanies Depersonalization.
Regarding physical symptoms, this under-activity can lead to difficulty with blood pressure, perspiration, circadian rhythm, heart rate, and appetite among other things. Dissociation also predicts violence in a wide range of populations and Depersonalization is found to be the most related to aggressive behaviors.  The Limbic regions are important for controlling emotions like anger and the over-regulation found in those suffering from DPDR may be a predictor in these aggressive behaviors.
There are no documented cures or treatment methods, but given the clinical presentations, there is strong evidence that these may be effective treatment methods.
- Increased Brain Activity:
- One of the Functional Hubs of our Default Mode Network is the Medial Prefrontal Cortex.  Activation in the Medial Prefrontal Cortex positively correlated with Depersonalization symptoms.  The DMN is a brain system active when individuals thinking about themselves, daydreaming, etc.  During attention demanding tasks, the DMN shows decreased activity, while structures comprising the brain’s main attention network, the Task Positive Network, show increased activity.  These two networks operate inversely. Given that, if a Functional Hub of the Default Mode Network is overactive, the Task Positive Network cannot be engaged. Those affected by Depersonalization often state they feel as if they are unable to feel present or like they are dreaming. The inability to engage this Task Positive Network in the face of emotional stimuli may explain this inability to be present.
- A Primary Hub of the Salience Network, the Dorsal Anterior Cingulate Cortex, also shows increased activity in Depersonalized patients.  The Salience Network drives switching between Default Mode and Task Positive Networks. 
- Decreased Brain Activity:
- One of the Primary Hubs of the Salience Network is the Anterior Insula. The core of the depersonalized state is rooted in a lack of anterior insula activity and clinical improvement in DPDR symptoms was associated with increased insula activity. 
- The Salience Network also contains Subcortical Limbic regions. Brain scans of Depersonalized individuals show diminished Subcortical Limbic activity.  These Subcortical structures contain regions like the Amygdala and Hypothalamus. Autonomic blunting and hypothalamic-pituitary-adrenal axis disregulation is present with Depersonalization as well.  The Amygdala is important for displaying emotions and emotional processing, while the Hypothalamus is important for regulating blood pressure, heart rate, and circadian rhythm among many other things. The hypo-arousal within these regions may explain the emotional difficulty and immune dysfunction that accompanies this disorder.
- The Salience Network drives switching between Default Mode and Task Positive Networks.  We can assume that while the Dorsal Anterior Cingulate Cortex is overactive, activity within the Insula and Subcortical regions must be increased in order to engage the Task Positive Network. Especially given that clinical improvement in DPDR symptoms was associated with increased insula activity. 
- Clinical Features:
- The Default Mode Network is responsible for constructing our sense of self and identity, and it’s activity is negatively correlated with activity within the Task Positive Network. A Functional Hub, the Medial Prefrontal Cortex, is overactive in DPDR patients.
- The Salience Network contains the Insula and many Subcortical Limbic structures, both of which are under-active in clinical representations of DPDR. The Insula plays an important role in both our Physical and Psychological pain response and the Limbic regions are critical aspects of our emotional personalities. Much of our emotional control, processing, and compartmentalization of short term memories take place here.
- Because these under-active Salient regions are responsible for switching between the Default Mode and Task Positive Networks, we can infer that this is reason individuals affected by DPDR cannot be present and feel as if they or their surroundings are not real.
- We can also infer that because brain regions responsible for constructing identity are overactive and regions that are responsible for emotions are under-active, the disconnect between these two is responsible for the alterations in identity and other impairments that are seen with Depersonalization Disorder.
Clinical improvement in DPDR symptoms is associated with increased insula activity.  Therefore, the treatment must focus on increasing activity within the Salience Network to reengage the Task Positive Network and refocus our attention to salient stimuli. Given that information, Fasting and Hyperthermic Conditioning may be some of the most effective ways of overcoming Depersonalization.
The full list of treatment options can be found on the Evidence Based Treatments page.
- Fasting and extended exercise promotes neuroplasticity (brain growth) and enhances functionality in our brain’s neural networks, as well as bolstering it’s resistance to stress, injury, and disease. Lifestyles consisting of three meals per day, plus snacks, and negligible exercise result in suboptimal brain functionality and increase the risk of major neurodegenerative and psychiatric disorders. 
- Intermittent Fasting could improve cognitive function and preserve the the brain against distress and could improve learning and memory. 
- The Salience Network has been shown to participate in feeding control, as Salient Network activity is reduced by a meal.  Prolonged fasts also affect Hypothalamic connectivity with the Dorsal Anterior Cingulate Cortex and Insula.  Therefore, extended periods without food may be helpful in increasing activity within the Salience Network.
*Consider consulting a doctor before fasting, especially with any preexisting conditions. Based on health conditions or lifestyles, fasting may not be for you and improper fasts can lead to potential long term damages. There are many resources available for those interested in Intermittent Fasting or Extended Fasting.
- Hyperthermic Conditioning
- The Salience Network, in addition to the Insula, contains structures like the Hypothalamus. The Hypothalamus is an important part of our adrenal response and Depersonalization Disorder has been associated with autonomic blunting and hypothalamic-pituitary-adrenal axis disregulation.  Therefore, increasing Hypothalamic activity may be helpful in overcoming DPDR.
- The Locus Coeruleus-Norepinephrine (LC-NE) System assists in mediating changes associated with attention reorientation and refocusing attention to salient stimuli.  The Locus Coeruleus is a Hypothalamic-pituitary-adrenal (HPA) excitatory brain region, promoting neuroendocrine and physiological responses. 
- Saunas and high intensity exercises may be helpful as they are effective ways of inducing heat stress. Heat stress significantly increases prolactin and norepinephrine secretion, which may be helpful in regulating the HPA axis.  
This information is using currently available data. DPDR impacts other brain regions that are not covered in depth within this analysis. Additional studies are needed to better understand the mechanisms and implications of Depersonalization Disorder, but this information can be used as a springboard for the overall understanding of how this impacts individuals affected by this.
Despite the need for additional studies and a better overall understanding, current evidence suggests that the treatment methods outlined on this website will be an effective starting place for overcoming Depersonalization Disorder.