Scientists has identified a circuit in the brain associated with psychiatric disorders

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A national team of scientists has identified a circuit in the brain that appears to be associated with psychiatric disorders ranging from overeating to gambling, drug abuse and even Parkinson’s disease.

“We discovered the brain connections that keep impulsivity in check,” said Scott Kanoski, a neuroscientist and associate professor at USC Dornsife College of Letters, Arts and Sciences.

“The key to this system is a neuropeptide that we’ve been focusing on, melanin-concentrating hormone, in studies on appetite and eating.”

The study was published Tuesday in the journal Nature Communications.

Melanin-concentrating hormone (MCH) is signaled by brain cells in a portion of the hypothalamus, a cone-shaped area of the brain that sits above the pituitary gland.

Research has indicated MCH is linked with appetite for food or drugs, but until now scientists hadn’t fully understood how it affects impulse control.

Can’t wait for donuts

The scientists conducted a series of studies on rats that demonstrated that impulsivity is a separate function from hunger and food motivation.

In one task, a rat could press a lever and receive a treat that Kanoski likened to a “little donut hole” that was high in fats and carbohydrates.

The release was timed, however, which meant the rat would have to wait 20 seconds to successfully press the lever and receive another one.

The rat would become eager and and would sometimes hit the lever before the time had passed, forcing the clock to reset and having to wait again for the next opportunity for a treat.

In another task, rats had a choice between two levers. One lever would release an immediate single treat. The other would release a batch of five treats—but every 30-45 seconds.

The rats would press the lever for the single treat more frequently than the other lever, even though it would have delivered far more food.

“They don’t just sit there and wait,” Kanoski said. “They worked harder to achieve the same, or even fewer, number of pellets.”

The struggle with impulsivity

The scientists tested lowering and raising the levels of MCH in the rats’ brains through various methods.

“We would drive the system up, and then we would see the animals be more impulsive,” Kanoski said.

“And if we reduced function we thought they would be less impulsive, but instead we found that they were more so. Either way, they had elevated impulsivity.”

Based on anatomical brain scans, the scientists were able to identify a neural pathway for impulse control.

Neurons in the lateral hypothalamus signal MCH to other neurons in the ventral hippocampus, an area of the brain associated with emotions, memory and inhibitory control.

Kanoski said the next step is for scientists to map the link between the circuit for impulse control and the brain’s rewards system.

Such work could eventually lead to the development of better-targeted treatments for psychiatric disorders in which impulsivity is a core issue.

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Epidemiology

Psychiatric disorders are a huge problem in the United States and internationally. According to the American Psychiatric Association, about 25% of United States adults are diagnosed with a mental health disorder each year.

Disability caused by psychiatric disorders are overwhelming for patients, and the financial burden on the economy is immense. For example, based on a 2002 record, the cost of treatment of schizophrenia alone was about $63 billion[5]. About 20% to 30% of patients with schizophrenia are unresponsive to the antipsychotic therapy[6]. This is a considerable number of patients who will not be able to live a healthy life. While this describes cases of schizophrenia, similar inferences can be made about other mental health disorders.

Pathophysiology

The arrival of new diagnostic techniques and the ability to integrate information from different diagnostic modalities has made it possible for clinicians to understand the brain structure and function and help localize brain pathologies. Some of these diagnostic techniques include functional magnetic resonance imaging (fMRI), positive emission tomography (PET), neurophysiologic data from electroencephalogram (EEG), magnetoencephalography (MEG), transcranial magnetic stimulation (TMS)[7][8][9].

All these diagnostic modalities provide a more in-depth knowledge of brain activities and a stronger foundation for specific targets for neuromodulation surgery as a  treatment for some psychiatric disorders.

For example, researchers cite that the pathophysiology of OCD stems from abnormal function of the cortical-striatal-thalamic circuits, the genu of the corpus callosum has been strongly implicated in the pathophysiology of depression and schizophrenia, while the medial cingulate cortex has been involved in the pathophysiology of anxiety disorders[1][10].

History and Physical

While the advent of new diagnostic techniques and the ability to integrate information from different diagnostic modalities has made it possible to understand the brain structure and function and help localize brain pathologies, there are no tests or objective biological markers indicated as criteria for diagnosing a psychiatric disorder according to the Diagnostic and Statistical Manual of Mental Disorders (DSM)[11].  

Reliable diagnosis is based on the identification of symptoms, behaviors, personality traits among other features. While diagnostic tests can be used, in most cases it is to rule out other organic cause that may be presenting as a psychiatric problem.

A careful history and physical examination are fundamental tools for diagnosing and treating of psychiatric disorders.

Essential components of a patient’s history include present illness, past medical and psychiatric history, substance abuse, family and social information, and medication. This history will provide insight into patient’s current illness, predisposing factors like genetic vulnerabilities and low socioeconomic status, current life stressors, family dynamics, and support systems available to the patient. In some cases, medications that have worked for one family member may suggest that patient will benefit from it.

The physical examination usually starts with examining the general appearance of the patient and begins as the physician sets eye on the patient. The overall patient well-being and nutritional status may be assessed just through observation. For example, a patient with schizophrenia may appear disheveled or bizarre with clothing that may not be appropriate for the setting.

Other important aspects that can be assessed include the patient’s psychomotor activity, the patient’s mood and affect, and the patient’s thought process and thought content.

The clinician can observe whether the patient’s movements are delayed or if the patient is fidgeting and agitated.

The should evaluate patient speech pattern and determine if their thoughts are goal-directed or disorganized. Finally, assessing the patient’s thoughts for any delusions, hallucinations, or suicidal and homicidal thoughts, among others is essential.

Furthermore, a patient’s history can help guide the clinician’s physical examination as to what specific organ systems on which to focus their attention first.

For example, during an assessment of subconjunctival, a patient’s pale and dry appearance may be suggestive of self-neglect and inadequate dietary intake due to illnesses such as depression, schizophrenia, and anorexia nervosa.

Also, assessment of skin for any cuttings marks which may be associated with borderline personality disorder, depression and even some eating disorders. Other systems specific physical exams may be based on the history of the patient that gives the physician a prompt for further assessment.

Evaluation

As mentioned above, different diagnostic methods that help evaluate brain function are among the most critical advances that have made it possible to have targeted neuromodulatory psychiatric treatment. 

Some diagnostic techniques are good at giving information about the cortical structures and function.

For example, the transcranial magnetic stimulation provides a noninvasive means of probing the neurophysiology of different cortical structure cortical function and dysfunction and no information about the subcortical structure and function[7][8][9]. The fMRI and PET help provide information about the subcortical structures[7][8][9].

Treatment / Management

The primary goal of treatment of psychiatric disorders is to improve the functionality of the patients in the society. In schizophrenic patients, for example, this will mean decreasing the frequency and severity of the psychotic episodes.

While the stigma due to the history psychosurgery still looms, the utilization of neuromodulatory surgery to treat psychiatric disorder is backed by not only a more profound understanding of brain structure and function, but also, the development of new stereotactic microsurgical technique, and data about successful management of other neurological disorders through neuromodulation.   

This fountain of knowledge has led to the development of treatment options that target a particular region of the brain and with effects of these treatments that can be reversible, unlike the earlier process like prefrontal leucotomy that involves the permanent removal of parts of the brain.

The concept of deep brain stimulation in the treatment of psychiatric disorders can be attributed to DBS success in the treatment of movement disorder like Parkinson’s disease, essential tremor, dystonia[12].  

Current research has shown promising results in the use of DBS in treatment-resistant OCD, anxiety disorders, depression, and trials are underway for the utilization of this procedure in the treatment of schizophrenia[13]. DBS is a nondestructive treatment option that is reversible, less invasive, and treatment options can be modifiable based on the needs of the patients[14].

While cost wise DBS may be more expensive, recent studies show long-term benefits with cost leveling off[15]. DBS involves placing electrodes deep in the brain.

Through these electrodes, a specific region of the brain is stimulated with frequencies as high as >100Hz[16].

This often results in the inhibition of the target area producing some kind of functional ablation. The mechanism by which DBS exerts its effects is not entirely understood. It is believed that DBS modulates neural activity by stimulating or inhibiting neurons and fiber pathways that will allow subsequently neurochemical release[16].

For example, the stimulation of the inferior thalamic peduncle that connects the thalamus and the orbitofrontal cortex has been proven to help alleviate the symptoms of OCD[16].

Another neuromodulation surgery that has been reported to treat chronic and treatment-resistant depression is vagal nerve stimulation. Vagal nerve stimulation was initially developed to treat treatment-resistant epilepsy but later utilized for the treatment of depression[17].

This procedure involves the implantation of a device by a neurosurgeon or vascular surgeon under the chest that stimulates the left vagal afferent nerve fibers in the neck that helps modulates brain activity. T

he right vagus nerve is not stimulated because of its involvement in the actions of the heart[17]. The surgical and psychiatric side effects reported are rare and involve hypomania, mania and in some cases exacerbation of depression and increase suicide risk[17].

Other neuromodulation techniques that have been used for the treatment of psychiatric disorders that do not involve the application of a surgical device are Electroconvulsive Therapy (ECT) and Trans-magnetic stimulation(TMS). ECT has been widely reported in the literature as one the most effective treatment for chronic major depression and pharmacotherapy resistant major depression[18].

TMS on the other hand, often used for diagnostic purposes to assess brain function but also been cited for the treatment of psychiatric disorder like major depressive disorder[19]. While these methods are far less invasive than the neuromodulatory surgery and have been proven to be very useful, just like DBS and other ablative surgery, they are highly underutilized due to the stigma toward them.

Enhancing Healthcare Team Outcomes

Despite the advances in pharmacotherapy for treating psychiatric disorders like schizophrenia, anxiety disorders, obsessive-compulsive disorder, and depression, many patients become refractory.

A multidisciplinary team of nurses and physicians should be familiar with and educate patients and their families on the option of neuromodulation surgery as a last resort for the treatment of these patients.

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More information: Emily E. Noble et al. Hypothalamus-hippocampus circuitry regulates impulsivity via melanin-concentrating hormone. Nature Communications volume 10, Article number: 4923 (2019) DOI: 10.1038/s41467-019-12895-y


Journal information: Nature Communications
Provided by University of Southern California

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