Brain Scans Differentiate Suicidal from Non-Suicidal Patients with Bipolar Disorder
People with bipolar disorder are at high risk for suicidal behavior beginning in adolescence and young adulthood. A 2017 study by Jennifer A. Y. Johnston and colleagues in the American Journal of Psychiatry uses several brain-scanning techniques to identify neurobiological features associated with suicidal behavior in people with bipolar disorder compared to people with bipolar disorder who have never attempted suicide. Clarifying which neural systems are involved in suicidal behavior may allow for better prevention efforts.
The study included 26 participants who had attempted suicide and 42 who had not. Johnston and colleagues used structural, diffusion tensor, and functional magnetic resonance imaging (MRI) techniques to identify differences in the brains of attempters and non-attempters.
Compared to those who had never attempted suicide, those who had exhibited reductions in gray matter volume in the orbitofrontal cortex, hippocampus, and cerebellum. They also had reduced white matter integrity in the uncinate fasciculus, ventral frontal, and right cerebellum regions. In addition, attempters had reduced functional connectivity between the amygdala and the left ventral and right rostral prefrontal cortex. Better right rostral prefrontal connectivity was associated with less suicidal ideation, while better connectivity of the left ventral prefrontal area was linked to less lethal suicide attempts.
Marker of Heart Failure May Predict Brain Deterioration
A protein released into the blood in response to heart failure may be able to predict brain deterioration before clinical symptoms appear. The protein, N-terminal pro-B-type natriuretic peptide (NT-proBNP), is released when cardiac walls are under stress. High levels of NT-proBNP in the blood are a sign of heart disease. A 2016 Dutch study indicated that high levels of NT-proBNP in the blood are also linked to smaller brain volume, particularly small gray matter volume, and to poorer organization of the brain’s white matter. The study by researcher Hazel I. Zonneveld and colleagues, published in the journal Neuroradiology, assessed heart and brain health in 2,397 middle-aged and elderly people with no diagnosed heart or cognitive problems.
Researchers are working to clarify the relationship between cardiac dysfunction and preliminary brain disease, but researcher Meike Vernooij says it is likely cardiac dysfunction comes first and leads to brain damage. Measuring biomarkers such as NT-proBNP may help identify brain diseases such as stroke and dementia earlier and allow for earlier treatment and lifestyle changes that can slow or reverse the course of disease.
Fluctuations in White Matter in Adolescents with Bipolar Disorder May Indicate Cardiovascular Risk
During functional magnetic resonance imaging (fMRI) of the brain, data on physiological fluctuations in white matter are collected. These fluctuations are caused by cardiac pulses, cerebrovascular dysfunction, and other factors. Increasing fluctuations have been linked to cognitive impairment with age.
Vascular problems in adults with bipolar disorder have been linked to cerebrovascular disease, a group of conditions that affect bloodflow to the brain. In a recent study, researcher Arron W. S. Metcalfe and colleagues used data on physiological fluctuations in white matter (usually a nuisance variable) to assess the vascular health of teens with bipolar disorder. Compared to 32 age-, IQ-, and sex-matched controls, 32 adolescents with bipolar disorder had more fluctuations in white matter in three different clusters in the brain.
These white matter fluctuations are a possible early indicator of susceptibility to cerebrovascular disease in teens with bipolar disorder. Patients with depression and bipolar disorder are at increased risk for cardiovascular disease, so maintaining a good diet, exercising regularly, and assessing blood pressure, cholesterol, and lipid levels is recommended. See page __ where we describe research showing teens with bipolar disorder have stiffer artery walls.
Poverty Early in Life Decreases White Matter Integrity in the Brain
One-fifth of children in America grow up in poor families. Poverty can affect development, health, and achievement, and new evidence shows it even affects brain structure.
New unpublished research suggests that early poverty can affect the brain’s structure into adulthood. At a 2015 scientific meeting, researcher James Swain reported that socio-economic status at age 9 was associated with the integrity of white matter in several regions of the brain, including the hippocampus, parahippocampal gyrus, dorsolateral prefrontal cortex, ventrolateral prefrontal cortex, corpus collosum, and thalamus at age 23–25, regardless of income at that time.
The brain regions affected by childhood poverty support executive function (planning and implementation skills), social cognition, memory, and language processing. White matter provides the physical connections between parts of the brain, so damage to white matter may lead to problems with functional connectivity of the brain.
Schizophrenia: The Importance of Catching It Early
By the time psychosis appears in someone with schizophrenia, biological changes associated with the illness may have already been present for years. A 2015 article by R.S. Kahn and I.E. Sommer in the journal Molecular Psychiatry describes some of these abnormalities and how treatments might better target them.
One such change is in brain volume. At the time of diagnosis, schizophrenia patients have a lower intracranial volume on average than healthy people. Brain growth stops around age 13, suggesting that reduced brain growth in people with schizophrenia occurs before that age.
At diagnosis, patients with schizophrenia show decrements in both white and grey matter in the brain. Grey matter volume tends to decrease further in these patients over time, while white matter volume remains stable or can even increase.
Overproduction of dopamine in the striatum is another abnormality seen in the brains of schizophrenia patients at the time of diagnosis.
Possibly years before the dopamine abnormalities are observed, underfunctioning of the NMDA receptor and low-grade brain inflammation occur. These may be linked to cognitive impairment and negative symptoms of schizophrenia such as social withdrawal or apathy, suggesting that there is an at-risk period before psychosis appears when these symptoms can be identified and addressed. Psychosocial treatments such as individual, group, or family psychotherapy and omega-3 fatty acid supplementation have both been shown to decrease the rate of conversion from early symptoms to full-blown psychosis.
Using antipsychotic drugs to treat the dopamine abnormalities is generally successful in patients in their first episode of schizophrenia. Use of atypical antipsychotics is associated with less brain volume loss than use of the older typical antipsychotics. Treatments to correct the NMDA receptor abnormalities and brain inflammation, however, are only modestly effective. (Though there are data to support the effectiveness of the antioxidant n-acetylcysteine (NAC) on negative symptoms compared to placebo.) Kahn and Sommer suggest that applying treatments when cognitive and social function begin to be impaired (rather than waiting until psychosis appears) could make them more effective.
The authors also suggest that more postmortem brain analyses, neuroimaging studies, animal studies, and studies of treatments’ effects on brain abnormalities are all needed to clarify the causes of the early brain changes that occur in schizophrenia and identify ways of treating and preventing them.
Reduced Cognitive Function and Other Abnormalities in Pediatric Bipolar Disorder
At the 2015 meeting of the International Society for Bipolar Disorders, Ben Goldstein described a study of cognitive dysfunction in pediatric bipolar disorder. Children with bipolar disorder were three years behind in executive functioning (which covers abilities such as planning and problem-solving) and verbal memory.
There were other abnormalities. Youth with bipolar disorder had smaller amygdalas, and those with larger amygdalas recovered better. Perception of facial emotion was another area of weakness for children (and adults) with bipolar disorder. Studies show increased activity of the amygdala during facial emotion recognition tasks.
Goldstein reported that nine studies show that youth with bipolar disorder have reduced white matter integrity. This has also been observed in their relatives without bipolar disorder, suggesting that it is a sign of vulnerability to bipolar illness. This could identify children who could benefit from preemptive treatment because they are at high risk for developing bipolar disorder due to a family history of the illness.
There are some indications of increased inflammation in pediatric bipolar disorder. CRP, a protein that is a marker of inflammation, is elevated to a level equivalent to those in kids with juvenile rheumatoid arthritis before treatment (about 3 mg/L). CRP levels may be able to predict onset of depression or mania in those with minor symptoms, and is also associated with depression duration and severity. Goldstein reported that TNF-alpha, another inflammatory marker, may be elevated in children with psychosis.
Goldstein noted a study by Ghanshyam Pandey that showed that improvement in pediatric bipolar disorder was related to increases in BDNF, a protein that protects neurons. Cognitive flexibility interacted with CRP and BDNF—those with low BDNF had more cognitive impairment as their CRP increased than did those with high BDNF.
Neuropsychological Deficits After Concussion Are Correlated with White Matter Abnormalities
DTI brain scan can show damage to white matter following a concussion.
Many people suffer problems with mental functioning after an apparent concussion (otherwise known as mild traumatic brain injury, or mTBI) that does not show abnormalities on traditional brain imaging measures such as the MRI. New technology called diffusion tensor imaging (DTI) shows that the integrity of white matter tracts may be disturbed by concussions. White matter comprises parts of the brain where myelin wraps around axons, as opposed to grey matter, which reflects the presence of neuronal cell bodies.
In a longitudinal study published in the Journal of Neurotrauma, Vigneswaran Veeramuthu and colleagues compared 61 people with an mTBI to 19 healthy controls. The mTBI participants had their neuropsychological faculties assessed an average of 4.35 hours after their trauma, and participated in DTI scans an average of 10 hours after the trauma. Both the neuropsychological assessment and the DTI scan were repeated six months later. When the acute and follow-up assessments were compared to the same assessments in control participants, the two groups showed differences in numerous white matter tracts at the six-month mark. There was also an association between the degree of abnormality observed on the DTI scans and decrements in performance on the tests of neuropsychological functioning both immediately after the trauma and six months later.
The researchers concluded that their results “provide new evidence for the use of DTI as an imaging biomarker and indicator of [white matter] damage occurring in the context of mTBI, and [the results] underscore the dynamic nature of brain injury and possible biological basis of chronic neurocognitive alterations.”
Editor’s Note: People should be aware of these findings, which confirm earlier studies, and begin rehabilitative treatment as soon as possible after a concussion. New research should target white matter tract changes, with the goal of secondary prevention, i.e. limiting damage to the brain after a traumatic injury has occurred. There are several promising drugs that can prevent damage if administered immediately after an mTBI, including the antioxidant supplement N-acetylcysteine (NAC), which has shown promise in preliminary clinical and laboratory studies, and many others, including lithium and valproate, as reported by De-Maw Chuang and this editor Robert M. Post in a 2015 article in the Journal of Neurology and Stroke titled “Preventing the Sequelae of Concussions and Traumatic Brain Injury.”
Marijuana Addiction Associated with White Matter Loss and Brain Changes in Healthy People and Those with Schizophrenia
In an image from an MRI, the blue color depicts low blood volume, indicating areas of white matter.
It has been established that cannabis use is associated with impairments in working memory, but researchers are still investigating how these impairments come about. A 2013 study by Matthew J. Smith et al. in the journal Schizophrenia Bulletin compared regular marijuana users both with and without schizophrenia with demographically similar people who did not use marijuana.
Using magnetic resonance imaging (MRI), the researchers were able to map each participant’s brain structures. Healthy people who were marijuana users showed deficits in white matter (axons of neurons that are wrapped in myelin) compared to healthy people who did not use the drug. Similarly, patients with schizophrenia who used marijuana regularly had less white matter than those patients with schizophrenia who did not use the drug. There were also differences in the shapes of brain structures, including the striatum, the globus pallidus, and the thalamus, between cannabis users and non-users.
Differences in the thalamus and striatum were linked to white matter deficits and to younger age of cannabis use disorder onset.
Differences between cannabis users and non-users were more dramatic across the populations with schizophrenia than across the healthy populations.
Editors note: Future research is needed to determine whether marijuana causes these brain changes, or whether the brain changes are a biomarker that shows a vulnerability to marijuana addiction (although the latter is less likely than the former).
Other data show that marijuana is associated with an increase in psychosis (with heavy use), cognitive deficits, and an earlier onset of both bipolar disorder and schizophrenia in users compared to non-users. These findings make pot begin to look like a real health hazard. With legalization of marijuana occurring in many states, ease of access will increase, possibly accompanied by more heavy use. The most consistent pharmacological effect of marijuana is to produce an amotivational syndrome, characterized by apathy or lack of interest in social activities. Particularly for those already struggling with depression, pot is not as benign a substance as it is often thought to be.
Poverty Impacts Brain Development
In a 2013 study of children by Luby et al. in the Journal of the American Medical Association Pediatrics, poverty in early childhood was associated with smaller white and gray matter in the cortex and with smaller volume of the amygdala and hippocampus when the children reached school age. The effects of poverty on hippocampal volume were mediated by whether the children experienced stressful life events and whether a caregiver was supportive or hostile.
The children were recruited from primary care and day care settings between the ages of three and six, and were studied for five to ten years. They were initially assessed annually for three to six years and information on psychosocial, behavioral, and developmental dimensions were collected. Then the children took part in a magnetic resonance imaging (MRI) scan and continued annual assessments that included information such as whether the children experienced stressful life events.
Previous research has shown that poverty affects children’s psychosocial development and economic success in adulthood. This research shows that poverty also affects brain development. The findings suggest important targets for intervention that could help prevent these developmental deficits.
Youth at High Risk for Bipolar Disorder Show White Matter Tract Abnormalities
At a recent scientific conference, researcher Donna Roybal presented research showing that children at high risk of developing bipolar disorder due to a positive family history of the illness had some abnormalities in important white matter tracts in the brain. Prior to illness onset, there was increased fractional anisotropy (FA), a sign of white matter integrity, but following the onset of full-blown bipolar illness there were decreases in FA.
Roybal postulated that these findings show an increased connectivity of brain areas prior to illness onset, but some erosion of the white matter tracts with illness progression.
Editor’s Note: It will be critical to replicate these findings in order to better define who is at highest risk for bipolar disorder so that attempts at prevention can be explored.
