Spring arrived on March 20^th and it was hard to ignore. It was a hot day in Central Park with fellow New Yorkers rushing out to sit in the sun, play ball, or ride their bikes. In my hometown people rushed to the Bluff just to sit in the sand and stare off into the water of Long Island Sound. There were some die hard jet skiers that took the opportunity to get their jet skies into the water (even though the water was an icy 40 degrees). People are craving to be outside; to shake off the feeling that winter has left behind.

Here on Long Island we had a nasty winter. Every time it snowed it wasn’t  in inches, but in feet. We had record breaking amounts of  snow so when Spring came around the corner, we all rejoiced. For the last few weeks, the temperature has jumped into the 50s and 60s sometimes jumping into the high 80s.

A lot of changes happen once Spring arrives. Migrating birds return. The flowers bloom. The grass begins growing like a weed. But not all the changes are happening in nature. People are changing as well.

Have you ever heard of the winter blues? The winter blues is a set of symptoms closing resembling depression. These symptoms are present in the winter but commonly fade once warmer seasons arrive. Winter blues is another name for Seasonal Affective Disorder, or SAD. SAD is a mood disorder in which people who have normal mental health throughout most of the year experience depression symptoms in the winter months, repeatedly year after year. It has been estimated that 2-9% of adults suffer from SAD.

Those who experience SAD can experience difficulty waking up in the morning, a craving for carbohydrates, a lack of energy, and difficulty concentrating among other symptoms. When the spring comes, it is essentially a role reversal. Those who have been diagnosed with a form of depression in their past have a greater chance of experiencing these winter changes.

There have been some theories on why people suffer from SAD. There is depression, a chronic disorder characterized by depression symptoms all year round. But why have depression only during the winter months and be fine in the spring and summer? The answer may lie in studying other species including our past ancestors.

In many species, activity is diminished during the winter months due to less available food supplies and the difficulties involved in surviving during the cold weather. Several species like bears and box turtles, hibernate during the winter as an extreme way of surviving. A major clue resides in species that don’t hibernate, but still develop changes in their behavior during these less favorable times.

It can be argued that SAD is an evolved adaptation (like our fear of spiders and snakes). This adaptation in humans can be a variant of a hibernation response from an earlier ancestor. Since food was scarce during human prehistory, a low mood would reduce the need for the intake of calories, a good adaptation for the winter months.

If these theories are correct, then Seasonal Affective Disorder would not be a disorder as once assumed. Instead, it would be considered a normal response to colder seasons.

What did the study show?

Psychosis is a disordered cognitive state that can include disorganized thoughts, delusions, or hallucinations. It is a common symptom of schizophrenia and has been linked to a number of brain areas, including the the dorsolateral prefrontal cortex (DLPFC) and the hippocampus. Schizophrenia is also strongly associated with a number of genes, and a recent genome-wide association study identified a single nucleotide polymorphism in ZNF804A  as particularly important. Now, for the first time, a German research team has confirmed a link between ZNF804A and these brain structures. The group compared 115 participants who were either risk-allele carriers or non-risk-allele carriers and found differences in how their brains connect. For risk-allele carriers, connections were reduced within the DLPFC and also between left and right DLPFC . Conversely, risk-allele carriers showed increased connectivity between the DLPFC and hippocampal areas.

The study, primarily based at the University of Heidelberg, Germany, focused on a single nucleotide polymorphism (SNP) in ZNF804A (rs1344706)

Schizophrenia is a devastating, highly heritable brain disorder of unknown etiology. Recently, the first common genetic variant associated on a genome-wide level with schizophrenia and possibly bipolar disorder was discovered in ZNF804A (rs1344706). We show, by using an imaging genetics approach, that healthy carriers of rs1344706 risk genotypes exhibit no changes in regional activity but pronounced gene dosage–dependent alterations in functional coupling (correlated activity) of dorsolateral prefrontal cortex (DLPFC) across hemispheres and with hippocampus, mirroring findings in patients, and abnormal coupling of amygdala. , show that rs1344706 or variation in linkage disequilibrium is functional in human brain, and validate the intermediate phenotype strategy in psychiatry.

The study is important for a number of reasons. Firstly, it highlights the importance of connectivity (or dysconnectivity) as a neurobiological marker of schizophrenia. Secondly, it establishes ZNF804A as functional in the human brain. Thirdly, it is an example of how genome-wide association studies can align with anatomical data – to quote the authors, it affirms that “the pathophysiology of overt disease” can “mirror candidate gene effects”.

Functional Genomics and Big Picture Science

This third point is important to how we view science as a whole. Scientific research has traditionally relied upon reductionism as the primary means of discovery. To understand the world, reductionism tells us, we must strip it down to its barest elements. The sequencing of the human genome represents the ultimate triumph of this principle — the dis-assembly of an enormously complex living thing into its three billion molecular constituents. While unraveling the genomic structure ushered in a new era for biology and medicine, it laid bare a new problem—that of genomic function. Now that we have disassembled the machine, we have to figure out how to put it back together again.

Scientists have, in many ways, been forced to abandon reductionism and to look instead at the bigger picture – to see how things fits together. Increasingly we see large multi-disciplinary groups, each of which holds a different piece of the picture. In the current example, we have neuroimaging experts, who look at the gross structure of the brain, collaborating with geneticists, who look at m0lecules, and psychiatrists who look at behavior. These collaborations are exciting, because they integrate a number of different perspectives. Ultimately, this represents a triumph for “big picture” science.

What are PTSD and fMRI?

PTSD is an anxiety disorder commonly seen in individuals who have survived extremely stressful situations such as war, assault, or other events that lead to severe psychological trauma. There is some evidence of a genetic association – an intriguing paper by Binder et al. (2008) links PTSD with genetic polymorphisms at the stress-related gene FKBP5. A number of recent studies (e.g. Bryant et al., 2005) have used functional magnetic resonance imaging (fMRI) to link PTSD with specific brain networks including the anterior cingulate and amygdala. Dr. Morey’s group essentially replicates these findings, with PTSD patients showing greater activity in emotion-processing areas (the cingulate and amygdala are often associated with fear-processing) and reduced activity in the prefrontal cortex (often associated with vigilance and monitoring).

FMRI, the neuroimaging technique used by Morey’s group, uses a large magnet to monitor blood flow, which is very precisely related to activity in the brain.  When a region becomes active, there is an increase in blood flow to neurons, which leads to a very slight change in the magnetic signal. Although very slight, this change can be detected by extremely powerful magnets. By tracking magnetic changes in the brain, researchers can infer increased or reduced neural activity.

What is the evidence?

Every week, at least 3 or 4 neuroimaging papers report a neurological correlate to a particular emotion, behavior, or even voting preference. I recently interviewed Thomas Insel, Director of the National Institute of Mental Health (NIMH) and he made the point that despite over 19,000 neuroimaging publications in the last two decades, he could not point to a single neuroimaging study that affected practice, that changed the way we diagnose or treat any cognitive disorder. This, I think, is a very important point. There is no doubt that neuroimaging has potential, but, to date, its promise remains unfulfilled.

There is no grounds, therefore, for claiming that fMRI or any other neuroimaging technique can be used to diagnose PTSD. Accepted, the groups’ claims relate to future uses of fMRI, presumably an off-hand to an ill-informed news source. Nevertheless, this is an irresponsible comment given that there is currently no consensus among researchers about what the neural correlates of PTSD actually are. Sure, your study may have pointed to differences in prefrontal cortex and amygdala, but these areas are 1) associated with a host of executive and emotional processes, and 2) in the case of the prefronal cortex (or even the dorsolateral prefrontal cortex), extremely large and therefore unspecific.

Alzheimer’s disease is realistically the only cognitive disorder, where researchers have come close to developing a neuroimaging diagnosis. This is because Alzheimer’s has a very specific neuropathology that is clearly visible with autopsy. PTSD is absolutely different, any speculation linking PTSD to a neuroimaging diagnosis is distracting and misleading. When there are so many interesting science studies published each week, it is extremely disappointing to see stories such as this grab the limelight.

To conclude…

The short answer to my title question is a firm no. Maybe in the future it will be possible to make diagnoses of this kind, but we are currently not even close to this scenario. Any comments to the contrary are misguided, sensationalist, or downright untrue.