Psychology of Affective Disorders Lecture Transcript PDF

Module: Psychology and Neuroscience of Affective Disorders Week 1 Introduction to affective disorders Topic 1 Introduction to the complex world of mood - part 2 of 3 Dr Patricia Zunszain Senior Lecturer, Department of Psyc...

Module: Psychology and Neuroscience of Affective Disorders Week 1 Introduction to affective disorders Topic 1 Introduction to the complex world of mood - part 2 of 3 Dr Patricia Zunszain Senior Lecturer, Department of Psychological Medicine Lecture transcript Slide 3: We can use a series of approaches to understand affective disorders. Listening to patients is key. Similarly important is talking to their families. If we want to evaluate some possible underlying biological factors, we can look at the patient's blood, the saliva, hair, nails, urine, or fecal matter. For example in saliva we can look at the DNA sequence, we can follow DNA expression and we can measure certain molecules of interest. We can also use image and techniques to evaluate some aspects of the patient's brain. And compare observations from those in healthy controls. If we want to look at the specific brain tissues, there is a possibility of postmortem sampling. But in this case, we need to have in mind that most patients would have received some form of medical or psychological intervention after diagnosis. So we will get little insight into the pathogenesis of the disorders that may have started early in life. We can also prepare induced pluripotent stem cells, which contain the entire genetic background of the donor, though they have limitations if we want to study the role of the environment, as epigenetic changes are erased during the reprogramming process. We can use human cell lines. And we can use animal models which allowed to study disease progression and neuronal molecular pathways, though they cannot fully recapitulate all aspects of psychiatric disorders. So there is no perfect way to study, but we can improve our understanding with a combination of approaches. Slide 4: Affective disorders are frequently modeled using rodents, as both rats and mice can provide a series of behavioral readouts that can be used to assess these conditions. These animal models are particularly useful to enhance our understanding of the biological underpinning of the disorders. So they help us to look at brain-behavior relationships. Week 1 © King’s College London 1.  They are useful to identify new underlying pathways and new drug targets and also to test possible protective interventions. Slide 5: Researchers can use different inputs or procedures to elicit abnormal behaviors. Common environmental manipulations you will see in the studies include social isolation, unpredictable chronic mild stress, social defeat when a more aggressive animal is introduced, restrained stress or a physical manipulation, maternal deprivation, and also sleep deprivation. Slide 6: Another type of procedure is internal alterations, including some that are permanent as the olfactory bulbectomy and the adrenalectomy, that is, removing the olfactory bulb or the adrenal glands. And some that are transient, such as manipulation of the immune or distress system or disruptions induced by change in the diet. For example, removing tryptophan, the amino acid which is a precursor of serotonin. Researchers can also apply genetic modification, including transgenic and animals that have genetically altered certain systems. They can select extremes from an animal population, such as those with extreme aggression or anxiety. And they can also use inbred strains, and you are likely to come across many of these models papers. So it is important to be able to assess the quality of the data, and how translatable the data could be to the clinical conditions considered. Slide 7: We've seen that animals are used for certain genetic studies. Now if we want to look at genes for affective disorders, we can do that directly with patients. Now, why would we want to find genes that are useful to treat individuals with either unipolar or bipolar disorders? We can improve the diagnosis and the prognosis. Ideally, we'd want to predict this behaviors. We would want to identify severe cases so that we can intervene for high-risk groups. If we go into pharmacogenetics, we could hopefully be able to identify genetic variance that control the efficacy and possibly the adverse reaction to drugs. And all of these will also allow the development of new drug targets. Slide 8: What we know from genetic studies is that the genetic contribution to mood disorders is not the same for bipolar and unipolar depression. Studies have estimated the genetic contribution to unipolar depression is around 40% while the one for bipolar disorders is much higher and is between 80 and 90%. Week 1 © King’s College London 2.  Slide 9: The Psychiatric Genomes Consortium perform a genome-wide mega-analysis of over 9,000 cases and controls, found no single nucleotide polymorphism, or SMPs, reaching genome-wide significance, in contrast to a similar sample size of patients having schizophrenia or bipolar disorder. And one of the hypotheses for this lack of success is the underlying heterogeneity of the depressive conditions. None of the standards of divisions of data that were performed had interesting results. For example, will people look at recovering cases or cases under a certain age? So, if we can improve that, we can decide a certain starting age, results will probably be much better. In general, studies that try to identify the genetic contribution to depression have insufficient power, so that would involve increasing the sample size. Or we need to decrease heterogeneity by selecting cases of more homogeneous cases of depression. Slide 10: So I mentioned that one way to improve this situation of finding genes related to depression is to reduce heterogeneity. And this is what the Converge study did. In this case, they looked at all females, all cases that was single study. They have a consistent collection. They have very detailed information on environmental risk factors, and they look at recurrent depression in Chinese women. Most of them were in inpatient treatment, so clearly they were severe cases. And they looked at more than 5000 cases and 5000 controls. And this identified two regions with genome-wide significance on a particular chromosome, chromosome 10. And interestingly, this study was then replicated in a separate Chinese sample. Slide 11: Continuing with human studies, another way is to use imaging approaches. And there are two main different ones. There are structural ones and functional ones. If we want to look at the structure of the brain, we can use MRI, we can do CT scans or CAT scans, or we can do DTI, diffusion tensor imaging. Among functional studies, we have PET, SPECT and FMRI, Functional MRI, and they indirectly measure neuronal activity. We'd also have MEG and EEG that measure electrical activity. These techniques permit a closer look at the working brain. With FMRI, we can track changes that occur when a region of the brain responds to a certain task. With PET or SPECT we can look at the distribution and density of neurotransmitter receptors in certain areas. Week 1 © King’s College London 3.  Slide 12: For example, a two-center cross-sectional study look at the structural gray matter in participants from two independent sites. One group on Pittsburgh in Pennsylvania and the other one from Munster in Germany using magnetic resonant imaging. In the slide, you can see sagittal and coronal slices of the hippocampus and the amygdala, showing decreased grey matter volumes in individuals with bipolar disorder, compared with individuals with unipolar disorder. Slide 13: Imaging studies are used to evaluate treatment. In this slide, you can see changes after electroconvulsive therapy in patients with refectory depression who are scanned three times. Prior to ECT you can see green, after a second ECT session in blue, and within one week of completing the ECT treatment in pink, compared to the volume in healthy controls in light and dark orange. At the top of the slide, you can see the changes in hippocampal volume, while at the bottom of the slide, we can see changes in the amygdala. Patients show smaller hippocampal volume than controls at baseline. And both hippocampal and the amygdala volume increase with ECT and in relation to the improvement of symptoms. Slide 14: This understanding of effective disorders that we have been discussing so far is part of the data that the National Institute for Health and Care Excellence or NICE uses in the UK to produce guidelines for clinicians and healthcare practitioners. If you look at all the literature you may also see something which refers to the National Institute for Clinical Excellence. And that's the old name for NICE, but they're talking about the same thing. So NICE is is an executive public body of the Department of Health in the UK. If you're from overseas, you may not have heard of it. But basically, it helps clinicians to choose the best therapies for their clients. And it's based on looking at research and systematically evaluating the outcome of that research to decide which type of database have the best outcomes. NICE guidelines also have an important health economics component because we must consider not only which therapies are the most successful, but also which ones are the most successful in terms of economics. Week 1 © King’s College London 4.