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Authors: Dean Haycock

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A Remnant of Abnormal Development

Take a look at Figure 10. This half of a human brain was “fixed” or hardened and preserved in formaldehyde before being cut lengthwise down the middle. The front faces left so you are looking at the right hemisphere. You are also looking at a structure that may provide a marker for the development of psychopathy, the jelly-like material marked with an asterisk, the “septum.” The fluid-filled chambers or ventricles in the brain are separated by a transparent wall or enclosure. In Latin, that is septum pellicidum, the full anatomical name for this see-through membrane of nervous tissue.

Around three months after conception, a space or gap called a cavum (Latin for hollow) forms between the two sheets of the septum (see Figure 11). A couple of months later it normally begins to close and finishes closing three to six months after birth. The closing of the gap is related to the proper development of parts of the limbic system and other nearby structures. If the limbic system structures don’t develop normally, the gap doesn’t close. When this happens, the resulting condition is called cavum septum pellucidum (CSP).

Adrian Raine and his colleagues
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reasoned that looking for CSP in antisocial types would be a good way to find evidence that psychopathy and antisocial personality might be related to improper or flawed development of the brain, since complete development normally includes closing the gap. The presence of the gap is a marker for abnormal fetal brain development. But where can you readily find a supply of people with considerable psychopathic traits outside of a prison? Some people will swear they have psychopaths in their workplace, and they very well might, but the authors of this study turned to a temp agency instead.

Raine maintains that temporary employment agencies are good places to find psychopaths, as psychopaths often have a difficult time maintaining full-time employment. Based on one of his studies, he claims that 13.5% of those he tested were psychopathic based on the North American criterion of a score of 30 on the PCL–R diagnostic test. This estimate jumped to about one third of the temps if the European PCL–R cutoff of 25 was used. But why would psychopaths be hanging around temporary job agencies?

Raine suggests it is because they “provide wonderfully safe havens—almost a breeding ground.”
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The benefits for psychopaths may include the less-rigorous background checks typically given to temporary compared to permanent employees, and freedom of movement. The former lessens the risk for psychopaths that their past behavior will catch up with them, and the latter lessens the risk that their present behavior will. Temporary jobs allow them to pack up and leave after, or perhaps even before, they get caught exploiting, victimizing, or otherwise taking advantage of a temporary employer. Impulsivity is a frequent trait seen in people with high psychopathy scores, and changing jobs is easier at a temp agency.

The researchers used MRI to look for CSP in 87 persons recruited from temporary employment agencies. They found it in 19 of them. The
presence of the brain abnormality, according to Raine and his co-authors, is associated with more antisocial personality, psychopathy, and run-ins with the law compared to those people without the marker. This, they concluded, is evidence for neurodevelopmental involvement in later antisocial behavior.

Developing the Right Connections

If psychopathy is, as Raine and many other scientists believe, a neurodevelopmental disorder, then we might expect to see other signs of it in the structure of the brain. Since the function of the brain depends on its internal connections, the connections between two brain regions that both figure prominently in biological theories about the cause of psychopathy is a good place to look.

Many psychopathy researchers think they have a pretty good idea of what might be happening in the brains of psychopaths. The orbitofrontal cortex, especially the middle part (called the medial orbitofrontal cortex) in a normal brain suppresses the aggressive tendencies of the amygdala and prevents the entire interconnected network from recognizing and processing emotions and acting, or not acting, on them accordingly. If the orbital cortex or its communication pathways are hindered, the amygdala is free to promote its rather primitive agenda of animal-like passions, including different forms of aggression, violence, rage, and sexual promiscuity. At least it appears to do so in the most dangerous psychopaths.

The amygdala and the orbitofrontal cortex are connected by a bundle of nerve fibers called the uncinate fasciculus or UF. Uncinate fasciculus translated from Latin is “hooked small bundle”, which aptly describes the way it looks when you trace its path from the frontal cortex to the amygdala.

The prefrontal cortex, which includes the orbitofrontal cortex, and its connections to other brain regions are not completely developed until late adolescence. This has been offered as one reason some teenagers act “without thinking,” as some parents have noted. This part of the brain is involved in decision-making, solving problems, foreseeing the outcome of actions, and other “executive” tasks. It’s easy to imagine problems related to the development of this part of the brain and its connections contributing to psychopathic traits, including impulsivity.

Interfering with gene expression, environmental inputs or both can disrupt the normal development of the brain and its connections. Brain imaging studies suggest that inheriting genes linked to psychopathy might contribute to psychopathic behavior by affecting brain development before and after birth, according to Yu Gao, Ph.D., of the University of Pennsylvania and her colleagues.
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And there is plenty of time to alter this development. The brains of preschoolers quadruple in size. By six years of age, they are ninety percent on the way to reaching their final volume. Both gray and white matter in the brain continue to develop all the way into late adolescence.
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With this development come changes in behavior. Interfering with this development with something as drastic as abuse can indeed affect behavior.

All neurons communicate, sometimes making thousands of connections to other brain cells. It is not only the cell clusters and brain subdivisions that show signs of dysfunction in the brains of psychopaths; there appear to be problems with the wiring that connects brain regions closely involved in generating the characteristics that make humans humane.

Wiring in the nervous system consists of long extensions called axons. These neuronal extensions make contact and communicate with other neurons. The axons are covered by glial cells. Glia cover and insulate axons with a fatty covering called myelin. The fatty sheath is white. That is why neuroscientists call the communication pathways in the brain “white matter.” Clusters of neurons are referred to as “gray matter” to distinguish them from white matter.

Researchers at the Institute of Psychiatry at King’s College London used DT-MRI, or diffusion tensor magnetic resonance imaging tractography—the technique of choice for imaging fiber bundles in living subjects—to examine the connection between the amygdala and the orbitofrontal cortex in nine criminal psychopaths whose psychopathy (PCL–R) scores ranged from 25 to 34. These volunteers, ranging in age from 22 to 46 years, had been convicted of false imprisonment, multiple rape with strangulation, manslaughter, and murder. Their IQ scores ranged from 87 to 101. Nine healthy, non-criminal men of similar ages and IQ scores served as controls. The screening version of the Hare Psychopathy Checklist (PCL–SV) indicated they were not psychopaths.

The British scientists looked at the communication pathway between the frontal cortex and the amygdala, the uncinate fasciculus (UF). In the high-psychopathy group, the UF was broken down or structurally impaired. Furthermore, the degree of the structural problems in the UF was correlated with the degree of psychopathy in these psychopathic criminals.

The results indicate that the worse the quality of the connection between brain regions like the frontal cortex and others that process the ability to relate to others, the greater the psychopathic behavior.
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Although this British study was small, it is part of a growing and increasingly convincing body of research that links psychopathy to the interconnected regions that comprise the “emotional brain,” including the prefrontal-temporallimbic system. For example, Michael Koenigs, of the University of Wisconsin-Madison, and co-workers used DT-MRI to compare the connections in the brains of 14 criminal psychopaths to those in 13 non-psychopathic criminals. They too found evidence of reduced structural integrity in the UF connecting part of the frontal cortex (the vmPFC or ventromedial prefrontal cortex, to be exact) to the region of the temporal lobe that contains the amygdala. fMRI results provided further evidence that impaired connections between the vmPFC and the amygdala are a biological feature of psychopathy.
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These and other studies have found abnormalities in the communication pathways linking the frontal lobe with other brain regions and between the two sides of the brain.
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Scientists have also found differences in the thickness of the massive white matter bundle, the corpus callosum (Figure 11) that connects the right and left halves of the brain.
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It is through this massive bundle of connections that the two sides or hemispheres of the brain communicate with each other.

It looks as if, in the small-scale studies that have been conducted so far (nine to fifteen subjects), greater impairment of the connections between brain regions implicated in psychopathic behavior leads to greater psychopathy scores.

If the differences are related to mis-wiring of neuronal connections during development, no one knows for certain what causes them. In many, but not all, individuals with psychopathy, inheritance of unknown genes combined with stresses such as physical abuse during childhood are thought to be the major factors. It is possible that one or more of the hypothesized
genes that can influence a person’s susceptibility to psychopathy may have a role in guiding nerve-cell projections to their final targets before and after birth. Scientists suspect that this is a factor in the development of brain disorders like schizophrenia and autism. If psychopathy is actually a brain disorder and not a disturbing, disconcerting variety of personality that lies on the extreme end of the empathy spectrum, it is possible that the problem originates with faulty circuitry laid down in the fetal brain.

We are all born with far more neurons—billions more—than we end up with in our prime adult years. A few weeks after conception—brain cells are produced at an astounding rate, thousands per second, in a process called neurogenesis—you have plenty of brain cells, but neurogenesis doesn’t connect them. And it is the interconnections in the brain that give it its remarkable abilities.

The connections in much of the brain really start to form after an infant is born, during a dynamic process called synaptogenesis, which isn’t completed until young adulthood. This is when immature neurons “sprout.” The long, thin projections, axons, which will carry electrical signals between brain cells, seek out their targets to form synapses. These are the contact points between neurons where the electrical signal carried along the axon is converted into a chemical signal when neurotransmitters are released. These chemical messengers carry the signal across the gap in the synapse that separates one neuron from another. Synaptogenesis is influenced by both experience and genetics. This is one obvious place where something can go wrong in the brain’s development, resulting in serious consequences later in life.

At the end of an axon finding its way toward its synaptic target is a growth cone. This is an expanded, splayed-out extension of the axon, and it contains chemical sensors. These sensors respond to chemicals in the environment and use them to direct its progress. Watching its progress would be like watching the developing axon move through a three-dimensional map making turns right, left, up, and down based on the chemicals it senses in its immediate environment. The signals are received by proteins that stick out of the growth cones. These proteins act like antennas to pick up signals in the environment. Different proteins are produced at specific times during the migration process, based on instructions provided by RNA molecules.

If everything goes right, the RNA is degraded at the right time, after it has served its purpose by producing a specific protein needed at a specific time during the journey. Other RNAs, with precise timing, then produce other proteins which pick up different signals and continue to guide the axon to its proper target. Now, what if an RNA molecule hangs around too long, when it isn’t wanted or needed?

Scientists at the Weill Cornell Medical College in New York
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found evidence that this is where synaptogenesis can go wrong. Axons responding to signals they should no longer be responding to can take wrong turns. This can result in faulty brain wiring. The researchers investigated neurons traveling from the spinal cord into the brain, but the same mechanism could result in mis-wiring in other regions of the central nervous system.

This finding is consistent with reports that have been appearing since 2007 or so, which suggest that mutations that affect the control of RNA degradation can interfere with normal brain development. So far, these mutations have been associated with movement disorders linked to abnormal brain development.

It remains to be seen if problems with RNA degradation contribute to mental disorders that are believed to be related to faulty brain development. Even if they don’t, there are other key players in the formation of synapses that can be affected by mutations. For example, special cells that guide developing neurons in the neocortex produce a signaling molecule, another protein, called reelin.
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Some researchers believe problems with reelin signaling in humans might play a part in the development of schizophrenia, autism, depression, and Alzheimer’s disease. If psychopathy is indeed a developmental brain disorder influenced by genetics, as recent findings suggest, then it too might be added to the list of disorders like autism, major depression, bipolar disorder, attention deficit hyperactivity disorder, and schizophrenia that could be linked to faulty wiring in the brain.

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