How does the brain change in psychiatric disorders?
People who suffer from depression or schizophrenia are often also affected by other psychiatric disorders such as alcohol addiction or ADHD. Sabine Spijker, professor of Molecular Mechanisms of Cognition in Neuropsychiatric Disorders at Vrije Universiteit Amsterdam, studies how changes in those brain cells that are essential for memory and learning are brought about by these disorders.
“Psychiatric disorders are not only interrelated but are associated with cognitive malfunction such as problems in learning, memory, and flexibility”, prof. Spijker explains. “For example, people suffering from depression find it difficult to concentrate on a specific task. So do people with ADHD. People with post-traumatic stress disorder get repeated flash-backs of the traumatic events that give rise to their condition, and all kinds of stimuli in the environment of alcoholics could remind them of the kick they got from drinking.”
Genes and proteins
Together with her research team, prof. Spijker, who holds a position at the Centre for Neurogenomic and Cognitive Research (CNCR) of VU Amsterdam, researches the causality in altered neuronal expression of genes and proteins due to the pathological condition that is modelled in experimental animals. Spijker: “For example, we first examine altered protein expression in rats or mice in which we provoke depression. Subsequently, we find ways to restore these back to normal levels. In case we cure our animals, namely the disease symptoms measured are gone, this means that the protein is causal to the disease.”
Avoiding new encounters
The researchers measure many possible symptoms of the disorder at hand induced in these animals, such as an increased propensity to eat available food (a sign of impulsive behaviour), or avoiding an encounter with an animal they have not faced before (a sign of depression). They also measure symptoms indicative of loss of cognitive skills, such as the inability of the animal to find its way out of a maze or to remember where exactly an object (e.g. steel cylinder) was placed (both signs of loss of memory). “Together with measuring and intervening in the molecular changes in the parts of the brain responsible for learning, long-term memory and emotional control, this will help us to understand the mechanisms underlying these symptoms,” prof. Spijker adds.
Prof. Spijker and her team have already shown that impulsive behaviour (a sign of ADHD and schizophrenia) occurs more often in mice with high levels of the protein Neuregulin3 in the prefrontal cortex. This part of the brain plays a key role in memory and also in emotional control as seen in relapse to addiction. In a model of depression with comorbid alcohol abuse disorder they found that guanfacine, a drug prescribed for example to control high blood pressure, can reduce the motivation to take alcohol and alcohol relapse. Prof. Spijker’s group would like to investigate the feasibility of using this medication to help depressed men to combat their alcohol addiction.
Addiction rehab clinics
“We believe that our results could provide a firmer basis to generate improved medication, to create more understanding for psychiatric patients, and for a new approach to the care of certain classes of patients,” claims Prof. Spijker. “For example, addiction rehab clinics do not accept schizophrenics as patients at present because they do not wish to treat people with psychoses. On the other hand, psychiatric clinics don’t want to treat addicts. Basically, because they are not specialized in the disease that is comorbid. If we could show that these conditions are also molecularly related, this might help to bring about more understanding for these patients and their needs. And if we can learn more about the changes taking place in the brain at a molecular level as a result of these conditions, this might help in the development of new and more effective therapies.”