Neonatal Vitamin D Levels Influence Schizophrenia Risk

Both low and high concentrations of neonatal vitamin D were associated with increased risk of schizophrenia in an individually matched case-control study of a large Danish birth cohort.

Neonates with concentrations of 25 hydroxyvitamin D3 in the three lowest quintiles—as measured in dried neonatal blood samples—had a significantly increased risk of schizophrenia compared with those in the fourth quintile. Surprisingly, neonates in the fifth or highest quintile also had a significantly increased risk, according to a report in the September Archives of General Psychiatry. [...]

[S]imilar nonlinear U-shaped relationships (in which high and low concentrations are more significantly associated with an outcome than concentrations in the middle range) have been found between vitamin D and neonatal growth outcomes, and in some adult studies between vitamin D and cancer and cardiovascular disease.

The authors urged caution in the interpretation of the result, saying the U-shaped relationship could reflect underlying genetic predispositions requiring gene-by-environment studies to elucidate.

However, severely low concentrations of vitamin D have been associated with a range of disorders, including neurologic and neuropsychiatric disorders, and the current study strongly underscores the possibility of its involvement in some cases of schizophrenia, they suggested.

“Of particular interest to the hypothesis linking vitamin D deficiency and schizophrenia, the enzyme required for the production of [vitamin D] has now been identified in the human brain, and there is evidence from rodent models demonstrating that transient prenatal vitamin D deficiency results in persistent changes in adult brain structure, neurochemistry, and behavior,” the authors wrote. (via.)

Schizophrenia & immune activation

Researchers at the Swedish medical university Karolinska Institutet have discovered that patients with recent-onset schizophrenia have higher levels of inflammatory substances in their brains. [...]

Scientists at Karolinska Institutet have now been able to analyse inflammatory substances in the spinal fluid of patients with schizophrenia, instead of, as in previous studies, in the blood. The results show that patients with recent-onset schizophrenia have raised levels of a signal substance called interleukin-1beta, which can be released in the presence of inflammation. In the healthy control patients, this substance was barely measurable. [...]

“We would have made terrific progress if we were one day able to treat schizophrenia patients with immunotherapy, as it might then be possible to interrupt the course of the disease at an early stage of its development,” says Professor Engberg. (via.)

Cigarettes, Schizophrenia, Choline & Anterior Cingulate Cortex Dysfunction

The results showed that the nicotine-dependent patients had significantly decreased concentrations of the amino acid N-acetylaspartate (NAA) in the anterior cingulate cortex (ACC), the part of the brain that processes pleasure and pain. The decreased NAA levels were evident regardless of whether or not the patient used a nicotine patch and correlated directly with the patient’s smoking history: the greater the number of pack years (one pack per day for one year equals one pack year), the lower the NAA level.

“The ACC is involved in mediating conditioned reinforcement, craving and relapsing behavior in addiction,” said study co-author Christian G. Schütz, M.D., M.P.H., from the Department of Psychiatry at the University of Bonn. “Lower NAA levels have been implicated as indicators of neuronal or axonal dysfunction.”

Reduced NAA levels have been reported for a number of psychiatric and mood disorders, including schizophrenia, dementia and bipolar disorder, as well as in cases of substance abuse, particularly alcohol dependence.

Choline concentrations in the ACC were slightly lower in the smokers compared with the nonsmokers, and lower still in the female smokers compared with the male smokers.

Choline is significantly involved in cell membrane metabolism, which is essential for cardiac and brain function. Reduced choline levels can be a precursor to the breakdown of cell membranes. (via.)

Anterior cingulate cortex, religion, atheism, and more.

With two experiments, the researchers showed that when people think about religion and God, their brains respond differently—in a way that lets them take setbacks in stride and react with less distress to anxiety-provoking mistakes. Participants either wrote about religion or did a scrambled word task that included religion and God-related words. Then the researchers recorded their brain activity as they completed a computerized task—one that was chosen because it has a high rate of errors. The results showed that when people were primed to think about religion and God, either consciously or unconsciously, brain activity decreases in areas consistent with the anterior cingulate cortex (ACC), an area associated with a number of things, including regulating bodily states of arousal and serving an alerting function when things are going wrong, including when we make mistakes.

Interestingly, atheists reacted differently; when they were unconsciously primed with God-related ideas, their ACC increased its activity. The researchers suggest that for religious people, thinking about God may provide a way of ordering the world and explaining apparently random events and thus reduce their feelings of distress. In contrast, for atheists, thoughts of God may contradict the meaning systems they embrace and thus cause them more distress. (via.)

More on the anterior cingulate cortex, and in this case, specifically religious extremism:

Across all studies, anxious conditions caused participants to become more eagerly engaged in their ideals and extreme in their religious convictions. In one study, mulling over a personal dilemma caused a general surge toward more idealistic personal goals. In another, struggling with a confusing mathematical passage caused a spike in radical religious extremes. In yet another, reflecting on relationship uncertainties caused the same religious zeal reaction.

Researchers found that religious zeal reactions were most pronounced among participants with bold personalities (defined as having high self-esteem and being action-oriented, eager and tenacious), who were already vulnerable to anxiety, and felt most hopeless about their daily goals in life.

A basic motivational process called Reactive Approach Motivation (RAM) is responsible, according to lead researcher Ian McGregor, Associate Professor in York’s Department of Psychology, Faculty of Health. “Approach motivation is a tenacious state in which people become ‘locked and loaded’ on whatever goal or ideal they are promoting. They feel powerful, and thoughts and feelings related to other issues recede,” he says.

“RAM is usually an adaptive goal regulation process that can re-orient people toward alternative avenues for effective goal pursuit when they hit a snag. Our research shows that humans can sometimes co-opt RAM for short term relief from anxiety, however. By simply promoting ideals and convictions in their own minds, people can activate approach motivation, narrow their motivational focus away from anxious problems, and feel serene as a result,” says McGregor. [...]

Findings published last year in the journal Psychological Science by the same authors and collaborators at the University of Toronto found that strong religious beliefs are associated with low activity in the anterior cingulate cortex, the part of the brain that becomes active in anxious predicaments.

“Taken together, the results of this research program suggest that bold but vulnerable people gravitate to idealistic and religious extremes for relief from anxiety,” McGregor says. (via.)

Interestingly, according to Wikipedia (egads! check your sources, man!) the ACC also plays a role in empathy:

A large number of experiments using functional MRI, electroencephalography (EEG) and magnetoencephalography (MEG) have shown that certain brain regions (in particular the anterior insula, anterior cingulate cortex, and inferior frontal cortex) are active when a person experiences an emotion (disgust, happiness, pain, etc.) and when he or she sees another person experiencing an emotion.

There’s also this…

At the functional level, roles played by this region in communication include social bonding in mammals, control of vocalization in humans, semantic and syntactic processing, and initiation of speech. The involvement of the anterior cingulate cortex in social cognition is suggested where, for infants, joint attention skills are considered both prerequisites of social cognition and prelinguistic communication acts.

A few more tidbits on the ACC from Wikipedia:

The anterior cingulate cortex can be divided anatomically based on cognitive (dorsal), and emotional (ventral) components. The dorsal part of the ACC is connected with the prefrontal cortex and parietal cortex as well as the motor system and the frontal eye fields making it a central station for processing top-down and bottom-up stimuli and assigning appropriate control to other areas in the brain. By contrast, the ventral part of the ACC is connected with amygdala, nucleus accumbens, hypothalamus, and anterior insula, and is involved in assessing the salience of emotion and motivational information. The ACC seems to be especially involved when effort is needed to carry out a task such as in early learning and problem-solving. Many studies attribute functions such as error detection, anticipation of tasks, motivation, and modulation of emotional responses to the ACC. Rehearsing a task that originally produced spontaneous, novel responses to the point of producing rigid, stereotypic responses results in a diminished ACC response. [...]

Because the ACC is intricately involved with error detection and affective responses, it may very well be that this area forms the bases of self-confidence. [..] Whenever the dorsal area was active, fewer errors were committed providing more evidence that the ACC is involved with effortful performance. The second finding showed that, during error trials, the ACC activated later than for correct responses, clearly indicating a kind of evaluative function.[...]

There is evidence that damage to ACC is present in patients with schizophrenia, where studies have shown patients have difficulty in dealing with conflicting spatial locations in a Stroop-like task and having abnormal ERNs. Participants with ADHD were found to have reduced activation in the dorsal area of the ACC when performing the Stroop task. [...] There is evidence that this area may have a role in obsessive–compulsive disorder due to the fact that what appears to be an unnaturally low level of glutamate activity in this region has been observed in patients with the disorder, in strange contrast to many other brain regions that are thought to have excessive glutamate activity in OCD. Recent meta-analyses of voxel-based morphometry studies comparing people with OCD and healthy controls has found people with OCD to have [...] decreased grey matter volumes in bilateral dorsal medial frontal/anterior cingulate cortex.

Helen S. Mayberg and two collaborators described how they cured 4 of 6 depressed people — individuals virtually catatonic with depression despite years of talk therapy, drugs, even shock therapy — with pacemakerlike electrodes in area 25 (the anterior cingulate cortex). A decade earlier, Mayberg had identified area 25 as a key conduit of neural traffic between the “thinking” frontal cortex and the phylogenetically older central limbic region that gives rise to emotion. She subsequently found that area 25 appeared overactive in these depressed people — “like a gate left open,” as she puts it — allowing negative emotions to overwhelm thinking and mood. Inserting the electrodes closed this gate and rapidly alleviated the depression of two-thirds of the trial’s patients.[...]

Greater ACC activation levels were present in more emotionally-aware female participants when shown short ‘emotional’ video clips. Better emotional awareness is associated with improved recognition of emotional cues or targets, which is reflected by ACC activation.

From the Brodmann Area 25 (ventral ACC) Wikipedia article which should probably be merged into the “anterior cingulate cortex” page:

This region is extremely rich in serotonin transporters and is considered as a governor for a vast network involving areas like hypothalamus and brain stem, which influences changes in appetite and sleep; the amygdala and insula, which affect the mood and anxiety; the hippocampus, which plays an important role in memory formation; and some parts of the frontal cortex responsible for self-esteem.

One study has noted that BA25 is metabolically overactive in treatment-resistant depression and has found that chronic deep brain stimulation in the white matter adjacent to the area is a successful treatment for some patients. A different study found that metabolic hyperactivity in this area is associated with poor therapeutic response of persons with Major Depressive Disorder to cognitive-behavioral therapy and venlafaxine.

As few as 7 cups of coffee triples hallucination risk

Just cought this little blurb from an article at SciAm

If you’ve consumed a lot of caffeine—the equivalent to seven cups of coffee—you are three times more likely to hear voices than if you had kept your caffeine intake to less than a cup of coffee, according to psychologists at the University of Durham in England. Their recent study shows that overingesting the stimulant slightly increases your risk of experiencing other hallucinations as well.