Summaries on Psychopathology, it gives an insight in research that tries to unravel the mechanisms behind Psychopathology. This set of articles is based on the 2020-2021 course 'Understanding Psychopathology' at Groningen university.
Topics that will be discussed: mental illness, mental disorders, anxiety, depression, panic (disorder), psychotherapy, mental cognition, social psychology, phobias, addiction
Summary of the article The role of emotion regulation in autism spectrum disorder - Mazefsky et al. (2013)
Autism spectrum disorder (ASD) is a neuro-developmental disorder which is characterized by difficulties in social behavior and the presence of restrictive, repetitive behavior. There are some disruptions in the connections and processes of different brain areas. ASD is often accompanied by increased irritation, aggression, self-damaging behavior, anxiety and impulsiveness. Emotion regulation (ER) is a construct that can help to explain the problems that people with ASD experience. ER is defined as the automatic or intentional adjustment of one's emotional state to promote goal-directed behavior.
The definition of ER is not that clear. To understand ER better, it is important to distinguish between mood and emotion. Mood refers to a stable, long-term state, while an emotion is a reaction to a specific situation.
It is recommended to use different methods to study ER. Often, behavioral methods are used. For example, children have to wait for a reward or they are observed while they play together. However, this does not measure internal ER components. To measure internal ER components, interviews or self-reports (questionnaires) are used. Little research has been done into the psychometric quality of self-reports. Nor are self-reports suited for individuals who cannot speak, young children and people with intellectual disabilities. Biological measurements are also used to measure ER. For example, sometimes the heart rate variability is looked at, as well as fMRI. In the scanner, however, it is difficult to distinguish between an emotion and an attempt to regulate that emotion.
Research into ASD has focused more on emotional experiences than on ER. The results of the studies showed that ASD is associated with a poorly differentiated emotional response, more negative emotions, and limited cognitive insight. Children with ASD often use visible cues to determine their emotion (for example: I was sad because I was crying). Research suggests that there is not enough emotional insight to reach effective ER in ASD.
A possible explanation for the deficienties in ER in ASD could be the presence of another psychiatric disorder which causes the difficulties in ER. This explanation is plausible, because there is a reciprocal relationship between ER and psychiatric disorders: inadequate ER increases the chance of a psychiatric disorder, and having a psychiatric disorder interferes with emotion regulation. In addition, deficienties in ER are prevalent among many psychiatric disorders. However, it could also be the case that psychiatric disorders are too often diagnosed together with ASD. Another explanation is the presence of common risk factors. Deficienties in ER often goes together with anxiety, depression and borderline. Some mechanisms that can explain problems with ER in these disorders are also relevant for ASD. The tripartite model states that general stress is a shared risk factor between the disorders, but that physiological arousal is specific to anxiety, and anhedonia specific to depression. General stress also plays an important role in ASD, as well as physiological arousal. Therefore, treatments for ASD that focus on reducing this physiological excitement could be effective.
Normally, ER activates different areas of the prefrontal cortex (PFC). Research has shown that the PFC does not function normally in people with ASD. However, it is not yet clear whether there are any flaws in the connectivity between the PFC and the amygdala. It is clear that defects in the medial prefrontal cortex probably contribute to defects in ER in ASD. In the normal population, anxiety is associated with increased amygdala activity. With ASD, however, there is anxiety and reduced amygdala activity. However, other studies have shown increased activity of the amygdala. So, it is clear that the amygdala and the PFC are involved with deficienties in ER in ASD, but it is still not clear what the exact mechanisms are.
The functionalistic perspective states that someone is always consciously trying to regulate positive and negative emotions in order to achieve goals. Clinical observations in ASD show a tendency for people with this disorder to respond to emotional stimuli in a very intense manner. In ASD, there seems to be a lack of motivation for ER, which probably consists of poor emotional insight and self-monitoring. Adaptive ER strategies depend on the context, and are applied selectively. People with ASD also often experience problems with cognitive flexibility and behavioral adjustment, so it is not surprising that they make less use of adaptive ER strategies. Differences in information processing and perceptions in ASD can also contribute to this.
There are still many questions about the mechanisms that lead to deficienties in ER in people with ASD and therefore it is still unclear what the implications for treatment should be. The author of the article states that neural mechanisms that are shared with other psychiatric disorders in combination with ASD-related behavioral and cognitive characteristics together provide heterogeneous manifestations of ER problems in ASD. The author states that ER problems may be intrinsic to ASD, but that this may increase the risk of developing a comorbid psychiatric disorder. Research into ER must be done with the use of different methods, which preferably consists of a combination of physiological, neurological, and behavioral measurements. To understand ER in ASD, representative samples are needed with a variety of emotional expressions. Samples must also have different language and intellectual skills. Behavioral measurements are the most suitable for assessing ER in a clinical context, since this is independent of someone's language skills or cognitive functioning. These measurements can be looked at in combination with reports from parents or self-reports. Psycho-education about emotion regulation can also help to accept someone's problems and acknowledge someone's powers. There is some evidence that psychosocial interventions aimed at erupting ER outbreaks and negativity in children can be reduced, but much research is still needed. Measurements of ER that are reliable and valid for the full range of young people with ASD and that are sensitive to change have yet to be developed.
Binge eating disorder (BED) is characterized by recurring episodes of binge eating that occur without compensatory behavior. It is associated with a reduced quality of life and being overweight/obese. Binge eating episodes are characterized by a lack of control and imply difficulties in self-control processes. These difficulties suggest that mechanisms of cognitive and emotional dysfunction play a role in the development and maintenance of BED. Cognitive functioning (CoF) involves aspects of perception, thinking, reasoning, and remembering. Research has already shown that defects in CoF play a role in anorexia and bulimia nervosa. Emotional functioning (EmF) includes emotion regulation (ER) and emotional awareness (EA). Defects play a role in anorexia and bulimia nervosa. Research shows that binge eating episodes are linked to CoF and EmF processes. The escape theory states that cognitive processes are influenced by emotional states through a decrease of awareness when experiencing negative emotions. The ironic process theory states that cognitive processes influence emotional states when confronted with stressors. The purpose of this review is to critically summarize the current state of research on CoF and EmF in individuals with BED compared to 1) healthy controls and individuals with anorexia or bulimia, and 2) normal-weight and overweight/obese individuals without an eating disorder.
To be included in this study, studies had to: 1) include a sample of individuals with BED, 2) provide statistical comparisons with healthy controls, individuals with other eating disorders, or overweight people, 3) be published in English or German. Adult only samples were selected.
A total of 57 studies were used. The majority of studies featured an all female sample.
There were 12 studies of CoF with neutral stimuli. In six studies, inhibition was measured including the Stroop color-word task and a Stop Signal Task, among others. No differences were found between individuals with BED and obese people or people with normal weight. Four studies measured flexibility using neuropsychological tests. In one study, subjects with BED took longer to complete a task than people with normal weight or people who were obese, but this did not apply to two other studies. The results were therefore heterogeneous, depending on the study and the tasks that were used. Working memory was investigated in two studies. The results were inconsistent for verbal working memory, and individuals with BED did not differ from an obese control group regarding visual working memory. Verbal memory was investigated in one study, and no differences were found between BED and obese people. Decision making was investigated in five studies, with inconsistent results. Regarding delay of gratification, no differences were found between the BED group and the obese/normal weight control group. Regarding planning and problem solving, obese individuals with BED achieved lower outcomes and made more mistakes than obese controls.
People with BED showed reduced prefrontal and insular processing in a Monetary Loss Task in comparison to obsese/normal weight controls. Obese controls showed increased ventral stratial and prefrontal activity compared to normal weight controls. During the Stroop Task, people with BED exhibit diminished activity in the prefrontal cortex, insula and frontal gyrus compared to obese/normal weight controls.
Obese individuals with BED reported more difficulty in overriding or changing dominant inner responses and interrupting undesired behavioral tendencies compared to obese/normal weight controls.
In terms of attention and flexibility with food- and body-related stimuli, no differences were found between obese individuals with BED and obese and normal weight controls. BED is associated with inhibitions deficits in the context of disorder-related stimuli. They also experience more cognitive interference in working memory. People with BED also have a specific eating-related memory bias, and they remember fewer positive body-related words than people without BED. There are general difficulties in delaying gratification for people with BED, not just food-specific difficulties.
Obese individuals with BED show more ongoing and conscious attention allocation towards food stimuli than controls. They are also more focused on body parts that they see as ugly. Individuals with BED showed more frequent fixations of their own body pictures and less frequent fixations of control body pictures compared with overweight controls, while overweight controls demonstrated longer fixation of control body pictures than did individuals with BED. The activity in the orbitofrontal cortex is greater for individuals with BED, and there is reduced activity in the striatum and the ACC compared to controls. Obese individuals with BED also have a hyper-responsive reward system, with an increased release of dopamine, compared to obese controls.
Two studies looked at emotion regulation as a mediator in the link between negative emotions and eating behavior. Subjects had to watch videos that provoke negative emotions, and had to either suppress or reappraise those emotions. Suppressing emotions led to a desire to binge eat in individuals with BED, while reappraisal did not. Regarding interpersonal problem-solving ability, no differences were found with BED and overweight/obese controls regarding the number of generated relevant solutions. However, the solutions proposed by individuals with BED were significantly less effective and specific compared to those generated by controls.
A lower capacity to express positive feelings was associated with a higher probability of BED, and obese individuals with BED have a higher tendency to express anger. Two studies found that obese individuals with BED suppressed their emotions more often than the control group and used reappraisal less often. People with BED and anorexia nervosa report fewer positive thoughts and mindful observations. People with eating disorders show more self-criticism, difficulties with goal-directed behavior and impulse control. However, people with BED have fewer suicidal thoughts, difficulties with goal-directed behavior and impulse control compared to individuals with anorexia and bulimia nervosa.
Alexithymia occurs in 24.1% to 62.5% of people with BED, with a particular difficulty in identifying and describing feelings. People with BED also reported more problems with interoceptive awareness. In summary, it can be said that with regards to emotional functioning, individuals with BED 1) experience similar difficulties as individuals with anorexia and bulimia, but these difficulties are less severe with BED, 2) the difficulties are greater than those of obese/normal-weight controls.
Regarding CoF, obese individuals with BED did not differ from obese/normal-weight controls in tasks using neutral stimuli. However, when these tasks were performed with disorder-related stimuli, people with BED scored lower. In particular, there is an increased food-related reward sensitivity in BED, especially for high-caloric foods. There are also stronger responses in reward areas in the brain. More research is needed into the differences between individuals with BED and individuals with anorexia or bulimia. The increased sensitivity to rewards in the area of food, and deficiencies in delaying gratification, could impede people with BED to adhere to their plans not to eat certain foods or exercise more, and thus contribute to maintaining the disorder. People with BED also have a bias towards their own body and ugly body parts. People with BED also have difficulty with food-related response inhibition, and differences in prefrontal and orbitofrontal brain regions are visible. With regard to EmF, people with BED experience the same problems as people with anorexia or bulimia, but these problems are less serious with BED. Problems with emotion regulation can lead to binge eating in response to negative affect. People with BED might have deficits in differentiating between feelings and sensations of hunger/satiety which can induce emotional eating. The interaction between CoF and EmF has only been measured in one study, finding more disadvantageous decision making after increased negative affect.
Little is known about which specific aspects of CoF and EmF are altered in BED. Future research should investigate this. It is also difficult to determine whether changes in CoF and EmF are due to comorbid obesity or the increased eating disorder psychopathology in BED. The most important thing for future research, however, is to investigate the interaction between CoF and EmF in BED. There are also clinical implications. For example, interventions that focus directly on CoF could be used in the treatment of BED. Treatments that focus on attentional bias could also be promising. Regarding emotion regulation, there is already a treatment for BED that targets this, namely dialectical behavior therapy. Future treatments should focus on CoF and EmF, and not just on the main symptoms of BED and psychopathology.
Binge eating disorder (BED) is characterized by recurring episodes of binge eating that occur without compensatory behavior. Binge eating is characterized by a lack of control and implies difficulties in self-control processes. These difficulties suggest that mechanisms of cognitive and emotional dysfunction play a role in the development and maintenance of BED.
The escape theory states that cognitive processes are influenced by emotional states through a decrease of awareness when experiencing negative emotions. The ironic process theory states that cognitive processes influence emotional states when confronted with stressors.
The review at hand investigated the influence of cognitive functioning (CoF) and emotional functioning (EmF).
Regarding CoF, obese individuals with BED did not differ from obese/normal-weight controls in tasks using neutral stimuli. However, when these tasks were performed with disorder-related stimuli, people with BED scored lower. In particular, there is an increased food-related reward sensitivity in BED, especially for high-caloric foods. There are also stronger responses in reward areas in the brain. The increased sensitivity to rewards in the area of food, and deficiencies in delaying gratification, could impede people with BED to adhere to their plans not to eat certain foods or exercise more, and thus contribute to maintaining the disorder. People with BED also have a bias towards their own body and ugly body parts. People with BED also have difficulty with food-related response inhibition, and differences in prefrontal and orbitofrontal brain regions are visible.
With regard to EmF, people with BED experience the same problems as people with anorexia or bulimia, but these problems are less serious with BED. Problems with emotion regulation can lead to binge eating in response to negative affect. People with BED might have deficits in differentiating between feelings and sensations of hunger/satiety which can induce emotional eating. The interaction between CoF and EmF has only been measured in one study, finding more disadvantageous decision making after increased negative affect.
Future research should investigate which specific aspects of CoF and EmF are altered in BED, determine whether changes in CoF and EmF are due to comorbid obesity or the increased eating disorder psychopathology, and investigate the interaction between CoF and EmF. Future treatments should focus on CoF and EmF, and not just on the main symptoms of BED and psychopathology.
Major depressive disorder (MDD) is a disease characterized by a depressive episode lasting at least two weeks, with marked changes in mood, interest and pleasure, changes in cognition, and vegetative symptoms. It is twice as common among women as in men and it occurs in 6% of the total population worldwide every year. It increases the risk of diseases such as diabetes, heart diseases and strokes. It can also lead to death by suicide. The genetic contribution is probably 35%. MDD is associated with smaller hippocampal volumes and changes in either activation or connectivity of neural networks. The neurobiological systems that regulate stress are also altered, including the HPA axis, the autonomic nervous system and the immune system. 30% of people with depression do not recover after treatment.
Major depressive disorder (MDD) is a disease characterized by a depressive episode lasting for at least two weeks, with marked changes in mood, interest and pleasure, changes in cognition, and vegetative symptoms. It is twice as common among women as in men and it occurs in 6% of the total population worldwide every year. The median age of onset is 25 years. It increases the risk of diseases such as diabetes, heart diseases and strokes. It can also lead to death by suicide. 30% of people with depression do not recover after treatment and 80% experience a relapse.
The genetic contribution is probably 35%. MDD is associated with smaller hippocampal volumes and changes in either activation or connectivity of neural networks. The neurobiological systems that regulate stress are also altered, including the HPA axis, the autonomic nervous system and the immune system. There are also abnormalities in the affective-salience circuit and less activity in reward-related brain areas. There is increased activity in the default mode network, which contributes to excessive self-focus and rumination. Finally, there is hypo-connectivity in the frontoparietal cognitive control circuit, resulting in deficits in goal-directed attention.
Depressive symptoms might be induced by disruptions of neuroplasticity and neurogenesis, for example there are lower levels of brain-derived neurotrophic factor. It has been known for years that monoamines are involved in depression. Both tricyclic antidepressants (TCAs) and monoamineoxidase inhibitors (MAOIs) have clear effects on monoamine neurotransmitters.
First-degree family members of people with depression have a three times greater risk of developing depression. There is genetic overlap between depression and schizophrenia and bipolar disorder.
Stressful events are also related to depression, as well as adverse childhood events. Stress at a young age causes an increase in activity of neural circuits that contain corticotropin-releasing hormone. Stress in the womb also increases the risk of depression later in life.
Severity of depression can range from mild to moderate to severe. Specifiers for more specific diagnosis are: with anxious distress, mixed features, melancholic characteristics, with atypical features, with psychotic traits and with catatonic traits. Prevention of depression can be achieved by strengthening protective factors or tackling symptoms in a prodromal stage.
There are two treatment options: psychotherapy and pharmacotherapy. In general, moderate to severe depression is treated with medication or a combination of therapy and medication. A mild depression can usually be treated with only psychotherapy. The risk of relapse is smaller after psychotherapy. SSRIs and SNRIs are used more than TCAs because they have fewer negative side effects. The effectiveness is approximately the same for all types of antidepressant: 50%.
Treatment-resistant depression (TRD) is common in clinical practice (50-60%). In these cases it is important to assess medical and psychiatric comorbidity. Treatment methods for TRD are 1) psychopharmacological approaches, which use a combination of antidepressants or a combination of an antidepressant with another drug, or medication in high doses, 2) psychotherapy, mainly cognitive behavior therapy, 3) electroconvulsive therapy (ECT). However, ECT often leads to amnesia.
Depression can lead to impairments in functioning at work, in families and in cognition. The cognitive areas that are affected include executive functioning, memory and attention. The risk of suicide is 20 times greater in depression than in the general population.
Major depressive disorder (MDD) is a disease characterized by a depressive episode lasting at least two weeks, with marked changes in mood, interest and pleasure, changes in cognition, and vegetative symptoms. It is twice as common among women as in men and it occurs in 6% of the total population worldwide every year. It increases the risk of diseases such as diabetes, heart diseases and strokes. It can also lead to death by suicide. The genetic contribution is probably 35%. MDD is associated with smaller hippocampal volumes and changes in either activation or connectivity of neural networks. The neurobiological systems that regulate stress are also altered, including the HPA axis, the autonomic nervous system and the immune system. 30% of people with depression do not recover after treatment.
Depression occurs in 1 out of 6 adults. The prevalence appears to be independent of the income of a country. The discrepancy between countries is evident in terms of available resources and treatments. After puberty, women are twice as likely as men to develop depression. The median age of onset is 25 years. The absence of a partner and recent negative life events are determinants of depression. A range of social determinants as well as low educational attainment significantly increase the risk of depression. People who have experienced a childhood trauma have a more than twice as high risk of depression, with more severe symptoms, poorer course and worse treatment outcomes. The course of a depression is also worse if there are more serious symptoms or psychiatric comorbidity. An average episode lasts between 13 and 30 weeks. The chance of a relapse after a depressive episode is 80%. The contribution of depression to overall mortality is 10%.
There is not one mechanism that can explain all facets of the disorder. First-degree family members of people with depression have a three times greater risk of developing depression. There is genetic overlap between depression and schizophrenia and bipolar disorder. Many genes with small effects are involved.
Stressful events as well as adverse childhood events (including abuse, neglect, exposure to domestic violence or early divorce of parents) are related to depression. Stress at a young age causes an increase in activity of neural circuits that contain corticotropin-releasing hormone. Stress in the womb also increases the risk of depression later in life.
There are gene-environment interactions associated with depression, and they might involve epigenetic regulation. Changes in the HPA axis are associated with impaired cognitive functioning and are more common in severe depression and in the elderly with depression. Antidepressants lower the cortisol level over the course of treatment, but a meta-analysis showed that cortisol levels are the same before and after treatment in 50% of the cases. The evidence of HPA axis changes has not yet led to new therapeutic avenues. Studies show that inflammatory mechanisms can also play a role in depression. This is due to peripheral cytokines that affect the central nervous system. Depressive symptoms might be induced by disruptions of neuroplasticity and neurogenesis, for example there are lower levels of brain-derived neurotrophic factor. It has been known for years that monoamines are involved in depression. Both tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) have clear effects on monoamine neurotransmitters. However, it is remarkable that although medication affects these neurotransmitters a few hours after taking the medication, antidepressant effects only become visible after a few weeks.
Hippocampal volume is reduced in people with depression, but the question is whether this is already present in a first depressive episode or whether it develops later. Moreover, abnormalities have been found in the affective-salience circuit, which is a central part in guiding motivated behavior. This mainly concerns an overactive amygdala, anterior cingulate and anterior insula. On the contrary, there is less activity in reward-related brain areas, such as the ventral striatum. There is also increased activity in the default mode network, which contributes to excessive self-focus and rumination. Finally, there is hypoconnectivity in the frontoparietal cognitive control circuit, resulting in deficits in goal-directed attention.
Important differential diagnoses of depression are with bipolar disorder, persistent depressive disorder (depressive symptoms longer than 2 years), and schizophrenia. If the diagnosis of depression has been made, specifiers can be used, with the first being the severity. The severity can range from mild to moderate to severe. The second specifier is 'with anxious distress', and was introduced because patients with this specifier are more likely to report suicidal thoughts and have a less positive response to antidepressants. The 'mixed features' specifier indicates that during a depression there may also be symptoms on the other side of the spectrum that are associated with mania/hypomania. The 'melancholic characteristics' specifier includes the criteria anhedonia, lack of pleasure, loss of reactivity to positive stimuli, depression worse in the morning, waking up early, psychomotor disturbance, weight loss and excessive guilt. The 'with atypical features' specifier refers, among other things, to mood improvement in response to positive events, weight gain or increase in appetite and/or increased sleep. Finally, there are specifiers for psychotic and catatonic traits.
Given the high burden of disease of MDD, prevention is important and can be achieved by strengthening protective factors, or tackling symptoms in a prodromal stage.
There are two treatment options: psychotherapy and pharmacotherapy. In general, moderate to severe depression is treated with medication or a combination of therapy and medication. A mild depression can usually be treated with only psychotherapy. However, the preferences of the patient and treatment history must always be taken into account. Studies have shown that psychotherapy is effective, and that there are no major differences between different forms of psychotherapy. The effects of psychotherapy are similar to those of medication, but the risk of relapse is smaller after psychotherapy. Psychotherapy by telephone has also proven to be effective, and drop-out levels are lower. Group therapy is also an effective and cost-efficient form of therapy. Treatments via the internet, with coaching via the telephone, are also effective and are increasingly being used.
Antidepressants that act on monoamine neurotransmitters cause a neural response, and affect synaptic plasticity and gene expression. However, the precise way it works is still unknown. Nowadays, SSRIs and SNRIs are used more than TCAs because they have fewer negative side effects. The effectiveness is approximately the same for all types of antidepressant: 50%. Recently, antidepressants that are not based on monoamines are also being looked into. Several studies have shown that treatment with psychotherapy and medication is more effective than monotherapy.
TRD is a form of depression that does not respond to at least one antidepressant. It is common in clinical practice (50-60%). In these cases it is important to assess medical and psychiatric comorbidity. Variables associated with treatment-resistant depression are old age, marital status, long duration of the current depressive episode, moderate to high suicidal risk, comorbidity with anxiety, multiple admissions, and comorbid personality problems. Treatment methods for TRD are 1) psychopharmacological approaches, which use a combination of antidepressants or a combination of an antidepressant with another drug, or medication in high doses, 2) psychotherapy, mainly cognitive behavior therapy, 3) electroconvulsive therapy (ECT). ECT is the most effective and most widely used form of a non-pharmacological biological treatment for depression. However, it often leads to anterograde and retrograde amnesia. New treatments for TRD include repetitive transcranial magnetic stimulation (rTMS), deep TMS, magnetic attack therapy (MST), vagnus nerve stimulation (VNS) and deep brain stimulation (DBS). However, rTMS is less effective than ECT. New pharmacological treatments for TRD are treatment with ketamine or esketamine, antagonists of NMDA.
Depression can lead to impairments in functioning at work, in families and in cognition. The cognitive areas that are affected include executive functioning, memory and attention. There is an attentional bias towards negative information. There may also be impairments in psychomotor speed. The deficits in executive functions and memory can be permanent. Neurocognitive impairments are negatively associated with psychosocial functioning. The risk of suicide is 20 times greater in depression than in the general population. Antidepressants do not seem to reduce the risk of suicide, but this also depends on age.
Given the fact that depression is prevalent worldwide, the highest priority is to ensure effective treatments in low-income countries. Future research should focus on the interplay between the human genome and environmental factors. Research should also focus on distinguishing subtypes of depression so that specific treatments can be developed.
Personality develops from birth to adulthood. The persistent effect of personality disorders is often overlooked in clinical practice. Normal and abnormal personality are now known to be continuous across the life course. It is not stable, but it can change during life.
Personality disorders are seen as categorical constructs in both the ICD-10 and the DSM-5. This approach is criticized for arbitrarily separating normal from abnormal personality. Moreover, there is poor agreement between different diagnostic assessments. The full DSM-5 and ICD-10 systems are not widely used in either clinical practice or research, with their focus being largely restricted to borderline and antisocial personality disorder.
Progress in the understanding of personality and its relation to personality disorder across the lifespan is mainly due to research into personality assessment. Convergent validity between structured questionnaires, clinical interviews,self-reports and questionnaires has been poor. It was also often found during the assessment that there was comorbidity, both between different personality disorders and between personality disorders and other mental state disorders. In summary, there was a problem with the categorical conceptualization of personality disorders, not with the assessments themselves. Personality traits evident in childhood stabilise throughout life beyond age 30 years. These traits are 50% hereditary. It is not known exactly which genes play a role, but research is being done, for example, into the serotonin gene and into epigenetic mechanisms. There is a lot of clinical attention for borderline. It is important to recognize that psychopathological abnormalities also change when the personality changes, which changes the clinical picture. The authors of the article recommend that the medical community adopts a broad, life-course perspective on adaptive and maladaptive personality traits. This allows specific targets for treatment to be identified at different stages of life.
The study of the normal range of personality has led to a five factor model, known as the Big Five. The factors are Neuroticism, Extraversion, Agreeableness, Conscientiousness and Openness. These factors have strong psychometric properties.
Personality traits become consistent through exposure to a consistent environment, genetic effects, psychological makeup, the 'goodness of fit' between individuals and their environment and a strong sense of identity. Personality is moderately stable during childhood. This stability increases between adolescence and adult life, and changes more slowly from the age of thirty onwards. Personality further stabilizes until the age of sixty. The causes of these changes are unclear. Personality disorders change from childhood on in the same way as normal personality. There is continuity of personality disorders from adolescence to adulthood, so the disorder does persist. People with a personality disorder often change in the direction of improvement. Acute disruptions that occur in adults often lead to clinical presentations and lead to the mistaken belief that personality disorders only occur in adults. Poor functioning is often a stable characteristic, and can lead to the false belief that personality disorders are stable. Personality disorders have their roots in childhood and adolescence. However, sections of disorders in childhood and adolescence in the DSM or ICD do not mention personality disorder. Risk factors are adverse childhood experiences and maternal reports of anxiety, depressive symptoms and behavioral problems. It often becomes clinically apparent that there is a personality disorder during the transition between childhood and adulthood. This can interfere with achieving adult role functioning. The DSM and ICD indicate that it is highly unusual to diagnose a personality disorder before the age of 18, and also do not offer good diagnostic criteria for doing so.
The diagnosis in children and adolescents remains taboo, despite scientific evidence for validity. Many clinicians avoid giving the diagnosis on the grounds that they are protecting their clients against the stigma associated with the label. Clinicians, however, should be provided with good information that will help them to make clinically appropriate diagnoses of personality disorders without the fear of stigmatising patients. In section III in the DSM-5, an alternative personality disorder system is described, which removes age-related caveats for diagnosis.
Hardly any research has been done into age groups above 50 years. This is also due to problems in the criteria, which imply middle-age adult functioning, rather than the roles more common later in life. For example: the ability to keep a job is not really relevant for someone who is retired. People have different environments and roles later in life than when they were younger, which can aggravate or ameliorate maladaptive personality expressions. The stability of personality in older adults is overestimated, and they are more often ascribed a positive profile, with negative attributions related to physical rather than psychological characteristics. Observers also rate maladaptive personality traits less highly in older samples. So there is a bias towards minimizing personality problems later in life, which ignores the effects that traits like neuroticism and negative affectivity have on functioning later in life. Borderline in particular has an association with poor health later in life. Cognitive decline and Alzheimer's are also related to personality changes. More attention should be paid to personality issues in the elderly, as this entails a major health burden that is currently not visible.
Long-lasting outcomes are more likely to be achieved through changes in personality traits over time, as opposed to treatments solely targeting psychopathological abnormalities. Treatments must therefore focus on personality traits. Almost all references to mental health concern the treatment of mental state disorder. However, half of this also includes a personality disorder. If this is the case, the treatment outcome is often worse than if there is only a mental state disorder. Clinicians often do not recognize personality traits, or see them as persistent symptoms of the mental state disorder. Identifying personality factors in these types of cases can greatly influence the treatment chosen. A major difficulty is that little research has been done into interventions aimed at personality trait domains.
The greatest scientific and clinical challenge for a lifespan perspective is the need for a classification system that is clinically useful and scientifically robust. Such a system must show the dimensional nature of the characteristics that underlie adaptive and maladaptive personality. Scientific research must also be translated into clinically useful formats. Recognition of personality disorders in children and adolescents enables prevention, earlier detection, and implementation of evidence-based interventions with the aim of changing the life course of the personality disorder. More attention should also be given to the effect of personality disorders on mental state and physical disorders. A lifespan approach can also lead to less stigma and discrimination.
Personality develops from birth to adulthood. Both normal and abnormal personality are known to be continuous across the life course.
Convergent validity between different measurements determining personality disorder has found to be poor. In addition, comorbidity between different personality disorders and between personality disorders and other mental health disorders is highly prevalent. These issues are mostly ascribed to the categorical conceptualization of personality disorders. Even though both the DSM and ICD use this conceptualization, it is heavily criticized.
Personality traits evident in childhood stabilize throughout life beyond the age of 30 years. These traits are 50% hereditary. It is not known exactly which genes play a role. It is important to recognize that psychopathological abnormalities also change when the personality changes, which in turn changes the clinical picture. It is therefore suggested by the authors that treatment goals need to be re-evaluated at different stages of life.
The study of the normal range of personality has led to a five factor model, known as the Big Five. The factors are Neuroticism, Extraversion, Agreeableness, Conscientiousness and Openness. These factors have strong psychometric properties
Personality traits become consistent through exposure to a consistent environment, genetic effects, psychological makeup, the 'goodness of fit' between individuals and their environment and a strong sense of identity. People with a personality disorder often change in the direction of improvement. Acute disruptions that occur in adults often lead to clinical presentations and often lead to the mistaken belief that personality disorders only occur in adults. Poor functioning is often a stable characteristic, and can lead to the false belief that personality disorders are stable.
Even though personality disorders have their roots in childhood and adolescence, the DSM and ICD indicate that it is highly unusual to diagnose a personality disorder before the age of 18, and also do not offer good diagnostic criteria for doing so. Many clinicians avoid diagnosing children or adolescents with a personality disorder, because they want to protect them against stigma,
Little research has been done in age groups above 50 years. This is also due to problems in the criteria, which imply middle-age adult functioning, rather than the roles more common in later life. There is a bias towards minimizing personality problems later in life, which ignores the effects that traits like neuroticism and negative affectivity have on functioning later in life.
Long-lasting outcomes are more likely to be achieved through changes in personality traits over time, as opposed to treatments solely targeting psychopathological abnormalities. Clinicians often do not recognize personality traits, or see them as persistent symptoms of a mental state disorder. Identifying personality factors in these types of cases can greatly influence the treatment chosen.
The greatest scientific and clinical challenge for a lifespan perspective is the need for a classification system that is clinically useful and scientifically robust. Such a system must show the dimensional nature of the characteristics that underlie adaptive and maladaptive personality.
Personality disorders are common, influence the interaction between healthcare professionals and patients, are a strong predictor of treatment outcome, are a cause of premature death and are a great cost to society. Therefore, personality disorders must be an important part of any psychiatric assessment. The formal classification began when Kurt Schneider described a group of 'psychopathic personalities' in 1923. The classification included an essential core of personality disorder: the inability to form and maintain relationships. The requirements for the diagnosis of personality disorder are as follows: a pervasive pattern of maladaptive traits and behaviors that begin in early adult life and lead to significant personal distress and/or social dysfunction, and disruption to others. However, the description of specific personality disorders has always had a subjective component.
Diagnosing personality disorders is difficult. The disorder must be lifelong or at least of many years' duration and it must influence interaction with others. Another difficulty is that patients often do not recognize that they, and not others, are defective in their relationships. The DSM-5 review of the DSM-IV included a hybrid model to classify personality disorder, in which the severity was determined by the assessment of impairments in personal functioning. They also reduced the categories of disorders from 10 to 6, and assessed five areas of pathological personality trait domains. This was a major change from the categorical DSM-IV. However, according to the APA, this model was not yet ready for general use, and is therefore placed in a separate section of the DSM-5: Emerging Measures and Models. The DSM-IV classification was therefore retained, in which 10 categories are subdivided into three clusters. Cluster A includes the paranoid, schizoid and schizotypal categories. Cluster B includes the antisocial, borderline, histrionic and narcissistic categories. Cluster C includes the avoidant, dependent, and obsessive-compulsive categories. The three clusters are often used because there is a lot of comorbidity between the individual categories, which makes classification difficult, and because it is easier for researchers to consider 3 clusters than 10 disorders. Widiger and Simonsen saw that four dimensions cover the range of personality disorder: emotional disregulation, extraversion, antagonism and constraint.
Research in Western Europe and North America indicates a prevalence of personality disorders between 4 and 15%. Only one study has been conducted into international prevalence. This led to a 6.1% prevalence, with the lowest prevalences in Europe and the highest in North and South America. It is just as common among men and women, and just as common among ethnic minorities as majority populations. A quarter of primary health care patients have a personality disorder, and 50% of out-patient psychiatric patients. The highest prevalence is among people who have contact with the criminal justice system (75%). Because women seek help more often than men, they are overrepresented in clinical settings.
People with personality disorder have higher morbidity and mortality than those without. The higher death rate can be party explained by an increase in suicide and homicide. However, difficulties in relationships can effect relationships with care professionals, leading to misunderstandings, miscommunication and poor quality of care. Lifestyle factors such as smoking, alcohol and substance abuse are also important.
Personality disorders are rarely diagnosed in practice, and if they are, then the most assigned categories are borderline, antisocial personality disorder, or not otherwise specified. Few clinicians take the trouble to diagnose a personality disorder due to the complexity of the diagnostic system. However, there is also stereotyping, because people who show self-damaging behavior are almost automatically diagnosed with borderline and people who are aggressive and break the law are quickly diagnosed with antisocial personality disorder. One of the major difficulties with the assessment is the lack of fast, reliable tools. Most questionnaires tend to overdiagnose. Clinicians also have difficulty assessing and interpreting comorbidity in personality disorders.
If patients are identified as having between three and ten personality disorders, these are not separate disorders. Personality disorders are also comorbid with other mental disorders, such as depression or anxiety, so these disorders can dominate the clinical picture. However, personality disorders should not be seen as unimportant, as it may be one of the most important explanations for the recurrence of a disorder and difficulties in the treatment of a disorder. Yet, personality disorders are often forgotten as a target of treatment, often also because patients seek help for another clinical disorder and not for their personality disorder. In the DSM-5, the second axis of the DSM-IV has been removed because clinicians made too little use of it.
A radical change in classification has been proposed for the ICD-11. The main difference between the ICD-11 and DSM-5 is that the ICD focuses on the severity of personality disorders and does not retain the categories. The ICD-11 bans all type-specific categories of personality disorders, except the presence of a personality disorder itself. This is seen as a continuum, with varying severity. The first step in the ICD-11 in diagnostics is to identify whether there is a personality disorder. The second step is to identify the severity. A category can also be assigned if it is relevant, and it refers to a disturbance that might be manifest only intermittently, in specific circumstances, or in specific environments. One of the benefits of the ICD is that it removes the confusing comorbidity between the personality disorders. The ICD has no age limit for diagnosis, so in theory it can already be used with children. A 'late onset' qualifier is added to the ICD-11. This is necessary, because some people only show the disorder if protective factors are withdrawn. This can increase the prevalence in ICD-11 compared with ICD-10. The proposals for the ICD-11 are being tested by the WHO.
The core symptoms of personality disorders are: a pervasive pattern of maladaptive traits and behaviors that begin in early adult life and lead to significant personal distress and/or social dysfunction, and disruption to others.
Diagnosing personality disorders is difficult. The disorder must be lifelong or at least of many years' duration and it must influence interaction with others. Another difficulty is that patients often do not recognize that they, and not others, are defective in their relationships.
In the DSM-5, 10 different disorders are identified, in 3 different clusters. Cluster A includes the paranoid, schizoid and schizotypal categories. Cluster B includes the antisocial, borderline, histrionic and narcissistic categories. Cluster C includes the avoidant, dependent, and obsessive-compulsive categories. The three clusters are often used because there is a lot of comorbidity between the individual categories, which makes classification difficult, and because it is easier for researchers to consider 3 clusters than 10 disorders.
Research in Western Europe and North America indicates a prevalence of personality disorders between 4 and 15%. It is just as common among men and women, and just as common among ethnic minorities as majority populations. Women are overrepresented in clinical settings, because of a higher help-seeking behavior.
People with personality disorder have higher morbidity and mortality than those without, which can be explained by increases in suicide, homicide, unhealthy lifestyle behaviors and difficulties in relationships with care professionals.
Few clinicians take the trouble to diagnose a personality disorder due to the complexity of the diagnostic system. However, there is also stereotyping, because people who show self-damaging behavior are almost automatically diagnosed with borderline and people who are aggressive and break the law are quickly diagnosed with antisocial personality disorder. One of the major difficulties with the assessment is the lack of fast, reliable tools. Most questionnaires tend to overdiagnose.
Other mental health disorders can dominate the clinical picture when they are comorbid with personality disorders. Moreover, patients often seek help for another clinical disorder. Yet, it is important personality disorders are recognized and treated, as they may be one of the most important explanations for the recurrence of a disorder and difficulties in the treatment of a disorder.
The main difference between the ICD-11 and DSM-5 is that the ICD focuses on the severity of personality disorders and does not retain the categories. The ICD-11 bans all type-specific categories of personality disorders, except the presence of a personality disorder. This is seen as a continuum, with varying severity. One of the benefits of the ICD is that it removes the confusing comorbidity between the personality disorders.
Translating research results into treatment for personality disorders is difficult due to heterogeneous study populations and the different assessment criteria used in different studies. There is a lot of comorbidity with other mental disorders, and symptomatic improvement of a comorbid disorder is difficult to distinguish from true underlying personality change. Moreover, the essential features of personality disorders are difficult to measure. Yet the treatment perspectives are not as bad as previously thought, especially for borderline personality disorder. Effective treatments must have an effect on core symptoms and associated long-term social adaptation. Cluster A is the least treatable, cluster B has variable treatment outcomes, and cluster C is the most treatable.
The two main approaches in the treatment of personality disorders are psychosocial treatment and pharmacotherapy. Psychosocial intervention is recommended as primary treatment. Treatments range from rigorous behavior therapy to traditional psychoanalytic treatment. Different formats such as individual or group treatment are used. The severity of the personality disorder, the frequency of the sessions and the length of the treatment do not seem to be related to the treatment outcome. Siever, Davis and Soloff proposed four dimensions of psychopathology of personality disorders: affective instability, anxiety-inhibition, cognitive-perceptual disturbances and impulsivity aggression, which occur in all personality disorders. According to them, these dimensions should be studied and not the individual symptoms per disorder. There is no evidence for the validity of these dimensions, but the dimensions are used to measure the effect of medication. However, the effect of medication is hardly known because most research in this area has been done with borderline participants, and almost all are sponsored by the pharmaceutical industry.
Most individuals with a personality disorder have at least one other personality disorder. There is also often at least one axis I comorbid disorder (in particular depression, anxiety, and substance abuse). Depression is very common in borderline, and the response to antidepressants is lower for patients with comorbid personality disorder than for those without comorbid personality disorder.
Medication only focuses on specific aspects of a personality disorder, such as affective instability and cognitive-perceptual disturbances. Psychosocial treatment, mainly for borderline, aims to reduce acute life-threatening symptoms and improve distressing mental state symptoms. Research shows that the goal of reducing acute symptoms is often achieved, but that there is no improvement in the personality structure itself. The focus, context or the form of treatment does not seem to make any difference to these more complex outcomes.
People with cluster A disorders (schizoid, schizotypal and paranoid personality disorders) all experience social aversion, the inability to form close relationships and their relative indifference to these disabilities. They have poor self-awareness and empathic ability. They do not experience loneliness. Schizotypal disorder may be more related to schizophrenia than to personality disorders. People with a paranoid personality disorder are vigilant for the aggression and hostility of others, and are likely to perceive it even when it is absent. There is no good intervention for this. Patients with schizotypal personality disorder improve somewhat after using typical or atypical antipsychotics.
The cluster B disorders (borderline, antisocial, histrionic and narcissistic) share dramatic, emotional or erratic characteristics. Research focuses primarily on borderline and antisocial personality disorder. Previously, psychoanalytic therapy was mainly used in borderline, but nowadays more specific therapies are used. Dialectical behavior therapy and schema focused therapy are therapies that were adjusted for borderline. Psychoanalysis became transference focused, translating into transference focused psychotherapy. However, the problem is that borderline is common, and specialist treatments cannot be provided for all patients that admit to hospitals or are referred to outpatient care. These therapies also do not lead to improved social functioning. The different specialist treatments have the same effects, which drew attention to their common features. They are now deemed core requirements for effective treatments: a structured approach, patients are encouraged to assume control, therapists help to connect feelings and events and actions, therapists are active, validating and responsive, and therapists discuss cases with others. The APA guideline states that symptom targeted pharmacotherapy is an important adjunctive treatment for borderline. However, according to the NICE guidelines, medication should be avoided, except in crisis. Research shows that antipsychotics, SSRIs and mood stabilizers can be effective. Medication is often used in the treatment of borderline despite the lack of evidence.
Most of the research into antisocial personality disorder has been done on prisoners. Cognitive behavior therapy in combination with training in social skills and problem solving gave the best results in terms of recidivism. Early intervention could be important, because disruptive behavior disorders in adolescents are linked to antisocial personality disorder. Little research has been done on medication, but the guidelines of the NICE are that medication should not be routinely used for antisocial personality disorder, but can be be used for comorbid mental disorders.
A meta-analysis showed that cognitive and psychodynamic therapy had medium to large positive effects in the treatment of cluster C disorders, but it was unclear which disorder benefited most from the treatment. There has been no research into medication in the treatment of cluster C disorders.
Most research has been done on borderline, which makes it difficult to draw conclusions. Psychosocial therapy is effective, especially for borderline. Treatment should be a structured partnership where patients are encouraged to assume control over themselves. Therapists must be active, validating and responsive, and well supervised. Pharmacotherapy should only be used if it is integrated into psychosocial therapy and if it is used for a short time and in a symptom-focused way.
Translating research results into treatment for personality disorders is difficult due to heterogeneous study populations and the different assessment criteria used in different studies. Moreover, most research has been done on borderline, which limits generalization. There is a lot of comorbidity with other mental disorders, and symptomatic improvement of a comorbid disorder is difficult to distinguish from true underlying personality change. Moreover, the essential features of personality disorders are difficult to measure.
The two main approaches in the treatment of personality disorders are psychosocial treatment and pharmacotherapy. Psychosocial intervention is recommended as primary treatment. The effect of medication is hardly known because most of research in this area has been done with borderline participants, and almost all are sponsored by the pharmaceutical industry.
Most individuals with a personality disorder have at least one other personality disorder. There is also often at least one axis I comorbid disorder (in particular depression, anxiety, and substance abuse).
Treatments used for cluster A. There is no good intervention for people with paranoid personality disorder and their vigilance for aggression and hostility in others. Patients with schizotypal personality disorder improve somewhat after using typical or atypical antipsychotics.
Treatments used for cluster B. Research focuses primarily on borderline and antisocial personality disorder. As for borderline treatment, core requirements for effective treatments are: a structured approach, patients are encouraged to assume control, therapists help to connect feelings and events and actions, therapists are active, validating and responsive and therapists discuss cases with others. There is some evidence for antipsychotics, SSRIs and mood stabilizers being effective. Medication is often used in the treatment of borderline despite the lack of evidence. Cognitive behavior therapy in combination with training in social skills and problem solving gave the best results in terms of recidivism for antisocial personality disorder. Medication should according to NICE not be routinely used for antisocial personality disorder, but can be used for comorbid mental disorders.
Treatments used for cluster C. A meta-analysis showed that cognitive and psychodynamic therapy had medium to large positive effects in the treatment of cluster C disorders, but it was unclear which disorder benefited most from the treatment.
General comment: pharmacotherapy should only be used if it is integrated into psychosocial therapy, if it is used for a short time and if it is used in a symptom-focused way.
Somatization disorder, hypochondriasis, pain disorder and undifferentiated somatoform disorder that were in the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) have been removed in the new DSM-5. The DSM-IV diagnosis of somatization disorder required a specific number of complaints from among four symptom groups. This is not required in the criteria of somatic symptom disorder (SSD), but the physical complaints must cause significant distress, suffering, or they must disrupt daily functioning. In addition, they must be accompanied by excessive and disproportionate thoughts, feelings, or behaviors about these symptoms. To be diagnosed with SSD, the individual must experience symptoms continuously for at least 6 months.
Another important change in the DSM-5 criteria is that somatic symptoms do not have to be medically unexplained (as was the case in the DSM-IV). The explanation states that it is not justified to grant a person a mental disorder only when her/his complaints cannot be explained medically. In addition, whether the somatic symptoms can or cannot be explained, the individual must also meet the other criteria to receive a diagnosis of SSD. The DSM-5 criteria for SSD remove overlap and confusion that existed in the earlier editions. They encourage the clinician to provide comprehensive assessment of patients for accurate diagnosis and holistic care.
Most people with SSD are primarily seen in general medical settings. Therefore, the DSM-5 clarifies confusing terms and reduces the number of disorders and sub-categories to make the criteria more useful to non-psychiatric care providers. To ensure that the new criteria would indeed help clinicians better identify individuals who have SSD, scientists tested the SSD criteria in clinical practices during the DSM-5 field trials. The diagnostic reliability of the SSD performed very well. In the DSM-5, the emphasis is on the extent to which the patient has disproportionate or excessive thoughts, feelings, and behaviors about his or her somatic symptoms. The descriptive section on SSD notes that some patients with physical conditions, such as heart disease or cancer, may experience disproportionate and excessive thoughts, feelings, and behaviors related to their condition, and that these people therefore meet the criteria for SSD.
To be able to recognize whether a patient's thoughts, feelings and behaviors indicate a psychological disorder that can improve with the help of focused treatment, requires clinical training, experience and judgment, based on guidance such as that contained in the DSM-5 text. This shift in emphasis removes the separation of body and mind, as is still implied in the DSM-IV. Clinicians are encouraged to make a comprehensive assessment and use clinical judgment rather than a checklist, that may arbitrarily disqualify people suffering from both SSD and another medical diagnosis from getting the help they need.
The DSM-IV diagnosis of somatization disorder required a specific number of complaints from among four symptom groups. This is not required in the criteria of somatic symptom disorder (SSD) in the DSM-5, but the physical complaints must cause significant distress, suffering, or they must disrupt daily functioning. In addition, they must be accompanied by excessive and disproportionate thoughts, feelings, or behaviors about these symptoms.
Somatic symptoms do no longer have to be medically unexplained in the DSM-5 diagnosis. It is noted that patients with physical conditions may have disproportionate or excessive thoughts, feelings and behaviors about these symptoms. The DSM-5 has also reduced the number of disorders and sub-categories, so that it is easier to use in non-psychiatric settings. This is especially important for people with SSD, because most of them are primarily seen in general medical settings.
The diagnostic reliability of the SSD has performed very well.
The writers encourage clinicians to not separate body from mind in their assessments and to use clinical judgment rather than a checklist.
Summary of the article Gene–Environment Interactions in Severe Mental Illness - Uher, 2014
We include the most disabling psychiatric disorders that require inpatient treatment in severe mental illness (SMI). Examples studied in this article are schizophrenia, bipolar disorder, and severe depression. These disorders share a common etiology and therefore it might be beneficial to study these disorders together.
Both genetic disposition and environmental exposures can increase the risk of SMI. There is more contribution of genes to SMI than to common mental disorders. The heritability of schizophrenia and bipolar disorder is estimated between 70 and 80%. The heritability of depression depends on its severity: in the general population we find a low heritability of around 38% and in hospital-ascertained severe depression the heritability lies between 48 and 75%. Most genetic variants increase the risk of more than one mental illness.
There are multiple environmental factors contributing to SMI, such as in utero infections, lack of nutrients, maternal stress, perinatal complications, social disadvantage, growing up in an urban environment, ethnic minority status, childhood maltreatment, bullying, traumas and cannabis usage. Multiple factors contribute to each case of schizophrenia. Sometimes risk factors are correlated or act in synergy. However, it seems many cases of SMI can be prevented by modifying the environment.
When there is a gene-environment interactions, one or more genetic variants and one or more environmental factors causally contribute to the condition in the same individuals, in which genetic factors can influence the sensitivity to environmental exposures. This is different from correlations, in which genetic factors only influence the probability of environmental exposure. There is an interaction, when this term is significant in a multiple regression. However, statistical interactions are different from actual biological interactions. Therefore, multiple methods are necessary.
Some people are resilient against the environmental risk factors, and there are many individual differences as to the impact of the environmental exposure. This might, partially, be due to genetic factors. Many cases of SMI arise because of a synergy between genetic and environmental causes. Twin studies are done to examine the heritability of a disorder. The genetic component is computed by gene-environment interactions, in which the environmental factors are shared within a family. However this is a misattribution, because the strongest known environmental factors are shared within families, but twin studies estimate almost no or little contribution of shared environment. The heritability based on twin studies does probably depict a larger part of the variance than the genetic variants actually account for. These ‘heritability gaps’ suggest that gene-environment interactions might explain large part of the variance.
There seems to be a stronger link between low birth weight and low educational achievement for children of biological parents with schizophrenia than for children with no family history of SMI. Gene-environment interactions have an influence in the early processes on the neurodevelopmental pathway of SMI. Low birth weight, however, is not only a reflection of environmental factors during pregnancy, but also has a genetic contribution. Therefore the interpretation is more complex.
Another result found was that excellent parenting and clear communication can reduce the risk of schizophrenia, but only for offspring of biological mothers with schizophrenia. Furthermore, a serious infection during pregnancy increases the risk of psychosis in offspring with a family history of psychotic illnesses. Economic disadvantages during upbringing can increase the risk of psychosis in adoptees with a family history of SMI in biological relatives. Between family history of psychosis and childhood maltreatment a correlation was found. In a twin study of depression it was found that genetic disposition interacted with environmental triggers to result in depression.
These studies indicate that the pathogenic effect of many environmental factors depends on the genetic disposition to SMI. Adoption and twin studies have been used to separate the genetic and environmental effects. However, even in adoption studies there is still some sharing of environment in early life and in twin studies monozygotic twins may share more environment than dizygotic twins. Therefore the interpretation of gene-environment studies by proxy is limited. Familal relatedness is not the same as genetic contribution and environmental factors can interact with genetic variants.
Molecular genetic variants may help the development of novel indications for therapeutics. The first discovered gene-environment interaction for a psychotic disorder was that of the COMT gene. This gene codes for an enzyme that metabolises dopamine, which can result in the positive symptoms of psychosis. When valine is replaced by methionine at position 158, which is called a single nucleotide polymorphism (SNP), the enzyme is less efficient. A study showed that the risk of developing psychotic symptoms and disorders is higher in individuals with the efficient Val alleles when using cannabis in adolescence, while the less efficient Met allele offered protection.
This finding had a use impact on personalised prevention of psychosis. However, the finding has been difficult to replicate. It might have been a false-positive finding. Recent data, however, suggest the interaction really exist, but depends on the proportion of tetrahydrocannabinol and cannabidiol. The findings were replicated for adolescent cannabis use with high tetrahydrocannabinol to cannabidiol ratio. Another finding was the three way interaction between COMT genotype Val alleles, childhood maltreatment and adolescent cannabis usage in the etiology of psychotic experiences.
There also seems to be an interaction between de AKT1 gene and the use of cannabis in the development of psychosis, namely for the carriers of the C/C genotype on rs2494732. The finding has been replicated multiple times. Therefore it is highly advisable for individuals with this genotype not to heavily use cannabis. Another finding was that two polymorphisms in the GRIN2B gene interacted with maternal positivity for the herpes simplex virus-2. This finding still has to be replicated.
The FKBP5 gene sensitised individuals to develop post-traumatic stress disorder after being maltreated in childhood. It also increased the risk of psychotic symptoms. The polymorphism 5-HTTLPR of the SLC6A4 gene moderates the effects of childhood maltreatment on depression. The short alleles of 5-HTTLPR increase risk of developing persistent depressive disorder after childhood maltreatment. Another study found that the short 5-HTTLPR alleles and a history of childhood maltreatment was associated with cognitive impairment in people with psychotic disorders. This finding was only true for physical abuse and physical neglect, not for all childhood maltreatment forms together.
In the development of depression a functional polymorphism (Val Met) in the brain derived neurotrophic factor gene interacts with stressful life events and childhood maltreatment. The people with the Met allele have a higher chance of developing depression after exposure to adversity. In a student sample it was also seen that the people with BDNF Met allele and a history of childhood abuse were more inclined to developing psychotic-like experiences.
For bipolar disorders gene-environment interactions have not often been studied. There has been one study stating that the people with bipolar disorder and the BDNF Met allele were more likely to have depressive episodes after a stressful life event than the people with the Val allele.
When studying genes that are expected to be related to a disorder, a lot of genes can be overseen, since most genetic associations are found in genes that weren’t suspected to be involved. Gene-environment interaction searches across the genome might detect more genetic associations.
However, there has so far been only one such systematic search for gene-environment interactions in SMI. In this research they looked for genetic variants that sensitised individuals to developing schizophrenia when they were exposed to cytomegalovirus in utero. They looked at 29,000 polymorphisms that were significantly related to cytomegalovirus infection. The rs7902091 in the CTNNA3 gene significantly interacted with maternal cytomegalovirus infection in causing schizophrenia, but not with the accepted genome-wide level of significance. So it is not yet sure that this finding will be replicated.
More genome-wide studies should be done in the future. However we need large samples for this, because the statistical power is lower in these studies. There has been even less gene-environment research for bipolar disorder, than schizophrenia and depression.
Before we can use genome-wide gene-environmental studies some challenge have to be overcome. The environmental variables have to be accurately assessed with a high quality. The environmental variables to be assessed should also be carefully selected, because with each environmental variable added, the number of potential gene-environment tests increases by the number of genetic variables and the sample size has to increase as well.
To do studies with larger samples requires some coordination between genetic and epidemiological studies. It would be good to obtain the genetic and environment data from the same sample. That way, the total costs of the research won’t increase.
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