Task 6 - Having the Blues PDF

Task 6 - Having the blues Introduction Losses and failures are 2 types of events particularly important in triggering depressive episodes. Still, most people can shake off negative feelings within a few days or weeks af...

Task 6 - Having the blues Introduction Losses and failures are 2 types of events particularly important in triggering depressive episodes. Still, most people can shake off negative feelings within a few days or weeks after these events, and continue living product ively. However, for some people depressive symptoms linger and spread to all aspects of their lives - emotional, behavioral, cognitive & physical. This can result in diagnosable bouts of depression that are impairing enough to prevent someone from living a normal day -to-day life. Sometimes, depression can develop even without a precipitating life event, and will often persist for much longer than follow ing a loss or failure. Depression involves emotional, motivational, behavioral, physical and cognitive symptoms. Emotional: mostly experiencing negative emotions - being sad, hopeless, miserable & discouraged; being often close to tears and having frequent crying episodes; rarely experiencing positive emotions & displaying positive facial expressions; a significant loss of sense of humo r Anxiety is often experienced with depression, suggesting that many people experience a range of negative emotions that reflec t a single underlying symptomatology. Motivational: a loss of interest in & pleasure from normal daily activities or hobbies ( anhedonia); a lack of initiative & spontaneity; often reporting 'not caring anymore'. Lack of initiative may manifest itself in social withdrawal, reduced appetite & sexual desire. Behavioral: slowness of speech & behavior generally; becoming physically inactive; staying in bed for long periods; experienc ing periods of decreased energy & fatigue. Even the smallest tasks require substantial physical exertion. Depressed people often show characteristic postures and movements that are an integral feature of their depression experience (e.g. reduced walking speed, smaller amplitude of vertical movements). Exercise & mindfulness therapy focused on normalizing gait patterns in depressed patients has been shown to relieve depressiv e symptoms. Physical: sleep disturbances, such as middle insomnia (waking up during the night and having difficulty getting back to sleep), terminal insomnia (waking up early and being unable to return to sleep) & hypersomnia (indulging in increased daytime sleeping), headaches, indigestion, constipation, dizziness, and general pain. Cognitive: extremely negative views about self, the world and one's future, which generate pessimistic thinking, which in tur n leads to lack of initiative, involving impaired ability to think, concentrate or make decisions. The inability to affect the future also generated other problematic feelings, such as worthlessness, shame and guilt. Many depressed people develop the dysfunctional belief that others would be better off if they were dead, and this can often lead to transient but recurrent suicidal thoughts. There are 2 types of clinical depression: Major depression (a.k.a. unipolar depression) - characterized by extended periods of clinical depression which cause significant distress and impairment in functioning. Bipolar disorder - characterized by periods of mania that alternate with periods of depression. The extremes of these emotions are experienced i n ways that cause distress. Mania - an emotion characterized by boundless, frenzied energy and feelings of euphoria. Major depression Diagnosis, prevalence and comorbidity Psychopathology Page 1 Depression is a central feature of many anxiety & substance use disorders. Around 60% of people with depression also experience an anxiety disorder. Some have suggested that depression & anxiety are not truly independent disorders but represent subcategories of a larger gro up of emotional disorders with symptoms that can often intermix. There are several subtypes of major depressive episodes. Seasonal affective disorder - one of the types of depression - a condition of regularly occurring depressions in winter with a remission the following spring or summer. Main symptoms include depressed mood, lack of energy, hypersomnia, craving for carbohydrates, overeating and weight gain. SAD is developed due to higher secretion of melatonin during the extended periods of darkness in the winter, which makes people sleepy and less energetic. Premenstrual dysphoric disorder - a condition in which some women experience severe depression symptoms between 5 and 11 days prior to the start of the menstrual cycle. Symptoms improve significantly within a few days after the onset of the cycle. Symptoms are often a mixture of depression, anxiety and tension, and irritability and anger, which may occur in mood swings d uring the week before the onset of menses, improve once menses has begun, and become minimal or absent in the week post -menses. Physical symptoms are also reported: breast tenderness or swelling, bloating and weight gain, and joint and muscle pain. Can be successfully rerated with healthy lifestyle management (e.g. regular exercise & balanced diet), antidepressants or CBT. Chronic fatigue syndrome - characterized by depression & mood fluctuations together with physical symptoms (e.g. extreme fatigue, muscle pain, chest pain, headaches and noise & light sensitivity). Addressing cognitive factors with CBT improves symptoms. Prevalence of depression in American community samples range from 5.2% to 17.1%. Lifetime prevalence is 20% of men and 30% for women. Depression contributes 12% to the total burden of nonfatal global disease. There are cultural differences in lifetime prevalence that can be attributed to the following factors: ○ Stigmatization of psychopathology in many non-Western societies (e.g. Taiwan). ○ Higher levels of somatization in non-Western countries. ○ An element of subjectivity in measuring depression. ○ Recall failure with age (can account for the fact that lifetime prevalence rates decrease with increasing age cohorts). Women are almost twice as vulnerable to major depression than men and this is independent of cultural background. In the US, 18-29-year-olds are most likely to have had a major depressive episode in the past year. After these ages, the rates of depression decrease and in people over age 65 the rates are the lowest. However, rates of depression rise among people over age 85. When it does occur, depression in older people tends to be severe , chronic and debilitating. Psychopathology Page 2  debilitating. Older adults often have mild to severe cognitive impairment, which makes it hard to distinguish between a depressive disorder and the early stages of a cognitive disorder. There are a few explanations for the low rate of depression in older adults. Depression interferes with physical health, and thus people with a history of depression may be more likely to die before the y reach old age. As people age, they may develop more adaptive coping skills and a psychologically healthier outlook on life. People diagnosed with major depression lose an average of 27 work days per year due to their symptoms. Depression in workers costs employers an estimated $37 billion per year in lost productivity. More than 70% of people diagnosed with major depressive or persistent depressive disorder also have another psychological disorder at some time in their lives. Most common comorbidities are substance abuse, anxiety disorders, and eating disorders. Depression may cause or be caused by the comorbid disorder(s). Etiology Biological theories Heritability estimates of major depression range from 30% to 40%. The serotonin transported gene (SLC6A4) has been proposed as a candidate gene. People with abnormalities on this gene have an increased risk of depression when they face negative life events. Depression that begins early in life has a stronger genetic base than depression that begins in adulthood. Major depression is often associated with low levels of serotonin, dopamine and norepinephrine. Neurochemical theories of depression - depression is caused by low norepinephrine, serotonin or dopamine activity. Tricyclic drugs - drugs which block the reuptake of both serotonin and norepinephrine. Tricyclic drugs, SSRIs and monoamine oxidase inhibitors have been shown to alleviate depressive symptoms. The idea that depression results from low serotonin levels is simplistic. Other ideas include that depression is associated w ith an imbalance in neurotransmitters rather than deficits. Yet other theories state that low levels of serotonin interact with norepinephrine le vels in complex ways, so that combinations of low serotonin and norepinephrine produce depression, but low serotonin & high norepinephrine produces mania. Depression is associated with lower PFC activation & gray matter volume (particularly on the left side), which may result in the failure to anticipate incentives (motivational difficulties). Successful depression treatment is associated with increases in activity in the left PFC. Depression is associated with lower ACC activation, which may reflect a deficit in attention or the will to change (ACC activation is present during effortful emotional regulation that is required in situations where behavior is failing to achieve a desired outcome). Activity normalizes when people are successfully treated for their depression. Depression is associated with hippocampal dysfunction & lower volume, which is important for adrenocorticotrophic hormone secretion and learning about the context of affective reaction. Deficits may result in a dissociation between affective responses and their relevant contexts. This may manifest itself as feelings of sadness occurring independently of contexts in which such emotions are appropriate. Damage to the hippocampus may result from the chronic arousal of the body's stress response. The hippocampus contains many receptors for cortisol, and chronically elevated levels of this hormone may kill or inhibit the development of new neurons in the hippocampus. Treatment with antidepressants or anticonvulsive therapy leads in neural growth in the hippocampus in rats. Depression is associated with structural (higher volume) & functional (higher activation) abnormalities in the amygdala, which directs attention to affectively salient stimuli and prioritizes their processing. This results in prioritization of threatening information for negative processing and interpretation. Treatment for depression results in decreased amygdala activity. Hypothalamic-pituitary-adrenocortical (HPA) network - the biological system (hypothalamus + pituitary + adrenal cortex, connected with amygdala, hippocampus and cerebral cortex) that manages and reacts to stress, triggering the secretion of cortisol in response to stress. Normally, when we are confronted with a stressor, the hypothalamus releases corticotropin-releasing hormone (CRH) onto receptors in the anterior pituitary. This results in secretion of corticotropin into the bloodstream, stimulating the adrenal cortex to release cortisol into the blood. This process helps the body fight the stressor or flee from it. The hypothalamus has cortisol receptors - it detects increased cortisol levels and responds by decreasing CRH to regulate the stress response (therefore, this biological feedback loop calms the system when the stress is over). Depression is linked to elevated levels of cortisol & CRH, indicating chronic hyperactivity in the HPA axis and difficulty in the HPA axis' returning to normal functioning after a stressor. In turn, the excess hormones produced by heightened HPA activity have an inhibiting effect on receptors for the monoamine neurotransmitters (dopamine, serotonin & norepinephrine). People exposed to chronic stress may develop poorly regulated neuroendocrine systems. Then, exposure to minor stressors later in life leads to an overreaction of the HPA axis and its difficulty returning to baseline. This overreaction changes the functioning of monoamines in the brain, and an episode of depression is likely to follow. Psychopathology Page 3  This overreaction changes the functioning of monoamines in the brain, and an episode of depression is likely to follow. Also, chronic excessive exposure to cortisol may account for the volume reductions in the hippocampus, PFC and amygdala. Early traumatic stress (e.g. sexual/physical abuse, neglect, or other chronic stress) may lead to some neuroendocrine abnorma lities that predispose people to depression. Women who were sexually abused as children show altered HPA responses to stress as adults, even when they are not depressed. Children who have been abused or neglected show either exaggerated or blunted HPA responses. In animals, early stress promotes exaggerated neurobiological stress reactivity and vulnerability to depression. These vulner abilities can be reduced by providing the animals with subsequent supportive maternal care and/or pharmacological interventions. In women, changes in the ovarian hormones (estrogen & progesterone) affect the serotonin and norepinephrine systems and could affect mood. Hormonal changes of puberty, the menstrual cycle, the peripartum period, and menopause may trigger depression in women with a genetic or other biological vulnerability to the disorder. Inflammation may contribute to the experience of depression. Cytokines - proteins made by immune cells that control responses to foreign antigens & germs, generating inflammation and fever. Depression is associated with changes in the immune system, especially changes that involve cytokines. Both medically ill and medically healthy, but depressed individuals, show all main features of inflammation: higher cytokines , fatigue, cognitive dysfunction and impaired sleep. Animal studies show that administration of cytokines can profoundly affect the metabolism of serotonin, norepinephrine and do pamine and generate behaviors such as loss of appetite, lack of interest in socializing & sex, and increased sensitivity to pain. Psychological theories Psychodynamic approach - depression is a response to loss, in particular a response to the loss of a loved one (e.g. parent). Introjection - the first stage of this response to loss, where the individual regresses to the oral stage of development, which allows them to integrate the identity of the person they have lost with their own. It also allows them to direct all of the feelings they would have for t he loved one onto themselves (anger if they feel like the loved one 'deserted' them and guilt if they experience any positive emotions in the wake of the loss). The individual starts experiencing self-hatred that turns into low self-esteem. Psychoanalysis suggests that depression has a functional role because it returns the person to a period in their life (oral s tage) when they were dependent on their parents. This regression allows depressed people to become dependent on relationships with others and to utilize the of fered support. However, not every depressed person has lost a loved one. Symbolic loss - a Freudian concept in which other kinds of losses (e.g. a job) are viewed as equivalent to losing a loved one. These losses then cause the individual to regress to the oral stage and may trigger memories of inadequate parental support during childhood. Affectionless control (a type of parenting characterized by overprotection and lack of warmth and care) is related to risk of depression in adultho od. Individuals who report that their childhood needs were not adequately met by their parents are more likely to become depresse d after experiencing a loss. There is also a link between losing a parent and depression. It's hard to confirm the psychoanalytic theory because empirical evidence that is consistent with it is also consistent with other theories. Many elements of psychoanalytic theories are not falsifiable (e.g. introjection, oral stage fixation etc.). Behavioral theories states that depressive symptoms results from a lack of appropriate reinforcement for positive & constructive behaviors. This lead to the extinction of existing behaviors, and to a 'behavioral vacuum', in which the person becomes inactive and wit hdrawn. Depressed individuals report fewer rewards in their life than non-depressed individuals, and introducing rewards into the lives of depressed individuals helps to elevate their mood. Once the individual becomes depressed, their lack of initiative & withdrawal is likely to result in a vicious cycle, by contr ibuting to their lack of reinforcement, especially social reinforcement. Depressed individuals are more likely to elicit negative reactions in others, are less skilled in interacting with others, an d will usually communicate negative attitudes, appear withdrawn & unresponsive, and tend to demand reassurance. When interacting with depressed individuals, non-depressed controls show less positive social behavior. Interpersonal theories of depression - depression is maintained by a cycle of reassurance-seeking (that one is lovable and worthy) by depressed individuals that is subsequently rejected by family & friends because of the negative way in which depressed individuals talk about their problems. Their negative beliefs cause depressive individuals to doubt any reassurances they are given by friends and family, and this continues to annoy friends & family that do provide the reassurance. They easily perceive rejection by others (rejection sensitivity) and even when others give affirmations, they don't believe in them and anxiously keep going back for more. After a while, family and friends become weary of this behavior and may become frustrated. The insecure depres sed person picks up on these cues of annoyance and panics over them, leading to more insecurity and reassurance seeking. Excessive reassurance seeking in depressed individuals predicts future depressive symptoms. Excessive reassurance seeking is also associated with motivation to obtain self-confirming negative feedback, which is in turn a risk factor for depression and interpersonal rejection (vicious cycle). Depressed people are more likely than nondepressed people to have chronic conflict in their relationships with family, friend s and co-workers. Beck's cognitive theory of depression - depression is caused by biases in ways of thinking and processing information. Depressed people have developed a broad-ranging negative schema that leads them to view the world & themselves in a negative way. In turn, the negative schema influences the selection, encoding, categorization, and evaluation of stimuli in a way that leads to a vicious cycle of depressive affect & symptoms. Negative schemas are stable personality characteristics and are developed as a result of early adverse childhood experiences. Later in life, a stressful experience will reactivate negative schemas and generate biased thinking that generates depressive symptoms. The negative schemas have the structure of a negative triad = negative views of the self, world and the future. Psychopathology Page 4  future. This set of negative beliefs eventually generates self-fulfilling prophecies (e.g. because everything is interpreted negatively, initiative is not taken, and failure inevitably comes). The negative triad of beliefs also leads to several systematic thinking biases (see right). Support for negative thinking biases: Attentional biases to negative information in depressed people result in them prioritizing it. In the emotional Stroop task, depressed people are slower at naming the color of negative words than positive words, suggesting that their attention is drawn towards the meaning of such words. Depressed people also experience memory biases, recalling more negative words than positive words in memory tests. Usually the negative words are depression-relevant. Depressed people remember more negative than positive information about themselves, and they recall autobiographical memories in a biased way: more negative memories are recalled and the positive memories that are recalled are more general & less detailed. Depression is associated with more critical self-judgement and a raising of personal performance standards. Specific support for the theory: Dysfunctional negative beliefs in combination with a recent negative life event predict depression. Depressed individuals may have 2 different types of self-schema: A dependency self-schema, due to which losses trigger depression. A criticism self-schema, due to which failures trigger depression. It has also been suggested that depressed people are not pessimistic, but rather lack the optimism bias that mentally healthy people possess. Depressed people are much more accurate in experimental studies at evaluating how much control they have over a situation and the impression they made on others in a social situation. Learned helplessness theory - the type of stressful event most likely to lead to depression is an uncontrollable negative event. Such events, especially if they are frequent/chronic, can lead people to believe they are helpless to control important outco mes in their environment. In turn, this belief in helplessness leads people to lose their motivation and to reduce actions on their part that might con trol the environment as well as leaving them unable to learn how to control situations that are controllable. Reformulated learned helplessness theory - people who habitually explain negative events by causes that are internal, stable, and global tend to blame themselves for these negative events, expect negative events to recur in the future, and expect to experience negative events in many areas of their lives. In turn, these expectations lead them to experience long-term learned helplessness deficits as well as loss of self-esteem in many areas of their lives Hopelessness depression - develops when people make pessimistic attributions for the most important events in their lives and perceive that they have no way to cope with the consequences of these events. Pessimistic & hopeless attributional styles predict both first onset and relapse of depression. Rumination - a tendency to dwell on the experience of depression or its possible causes. Ruminating predicts the onset of depressive episodes and relapses into depression. In depressed people, rumination is driven by meta-cognitive beliefs that rumination is necessary in order to resolve depression. Rumination is a risk factor for depression during the transition from early to middle adolescence and is higher in women. Sociocultural theories Differences in the social conditions of demographic groups can lead to differences in depression vulnerability. 90% of people who commit suicide probably have been suffering from a diagnosable mental disorder. Mood disorders are most closely related to suicide, followed by borderline PD, substance abuse, anxiety disorders. The best predictor of future suicidal thoughts and behavior is past suicidal thoughts and behavior. Suicide risk is increased by a variety of stressful life events, especially events related to abuse, interpersonal loss, perceived failure, economic hardship, and physical illness. Interpersonal violence, especially sexual abuse, is the traumatic event most strongly linked to suicidal thoughts & attempts. Other predictors are loss of a loved one, physical abuse by a partner, economic hardship and physical illness (especially if it occurred early in life). Suicide contagion Suicide cluster - 2 or more (attempted) suicides that are nonrandomly clustered together in space or time. Suicide clusters are most likely among people who knew the person who committed suicide. Other clusters occur among people linked by media exposure to the suicide of a stranger, often a celebrity. It is possible that clusters occur due to suicide contagion, in which a suicide (attempt) makes the idea of suicide more acceptable and lowers inhibitions for suicidal behavior in people. Personality & cognitive factors in suicide Suicide is connected to impulsivity, hopelessness, cognitive rigidity, rumination, perfectionism and poor problem solving. Biological factors in suicide There is a strong evidence that suicidal behavior is heritable. Suicide is linked to low serotonin and abnormalities in genes that regulate serotonin. Treatment and prevention Treatment of suicidal persons Community-based crisis intervention programs are available to help suicidal people deal in the short term with their feelings and then refer them to mental health specialists for longer-term care. SSRIs and lithium can reduce the risk of suicide. Dialectical behavior therapy (DBT) and CBT can reduce suicidal thoughts and behaviors. Suicide prevention Suicide hotlines and crisis intervention centers provide help to suicidal people in times of their greatest need, hoping to prevent a suicidal act until the suicidal feelings have passed. Some programs also aim to educate entire communities about suicide, but evidence supporting this is mixed, because people who are not suicidal may start seeing suicide like an understandable response to stress. Studies of school-based suicide prevention programs have found that adolescents who had made prior suicide attempts generally reacted negativel y to the programs, saying that they were less inclined to seek help after attending the program than before. Not fade away: the HPA axis and depression - Cowen (2010) Use of salivary cortisol to assess HPA axis activity Salivary cortisol measurements allow the sampling of large numbers of participants in ecologically valid conditions. In subjects with depression, there is an increase in salivary cortisol upon waking up. Trait or state? The increase in waking salivary cortisol found in acutely depressed patients seems to have trait-like characteristics. Secretion is higher in patients recovered from depression and is also abnormally high in people with no history of the disord er but who are at increased risk because of high neuroticism scores or a parental history of depression. Therefore, although some aspects of HPA axis abnormality resolve with improvement in depressive symptoms, others are more per sistent and may be present before the onset of clinical illness, thereby representing a vulnerability marker. Elevated salivary cortisol secretion is predictive of future depressive episodes in both young people and adults. Waking salivary cortisol has high heritability. In non-human primates, it may become abnormal due to early separation of children from their mothers. Children of mothers with postnatal depression show cortisol hypersecretion and although genetic factors could play a role, it is equally possible that disturbances in early attachment associated with the presence of maternal depressive symptoms could lead to abnormal HPA axis development. Cortisol and the brain Elevated cortisol secretion may result in depressive symptoms through several mechanisms. Hippocampal neurogenesis is inhibited by excessive cortisol secretion. Patients with recurrent depression show hippocampal at rophy, which could be a long- term consequence of excess cortisol secretion. Cortisol has negative effects on cognitive function, which may contribute to difficulties (e.g. in problem -solving), thereby increasing the risk of affected individuals encountering adverse environments. Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene - Caspi (2003) Psychopathology Page 11 Introduction The short ("s") allele in the 5' regulatory region of the 5-HTT gene (5-HTTLPR) is associated with lower transcriptional efficiency of the promotor compared with the long ("l") allele. Variations in the 5-HTT gene moderate psychopathological reactions to stressful experiences through a G x E interaction. In rhesus macaques, the s allele is associated with decreased serotonergic function among monkeys reared in stressful conditi ons, but not among normally reared monkeys. Humans with 1 or 2 copies of the s allele show greater amygdala activity to fearful stimuli compared to individuals homozygou s for the l allele. Method In this study, the G x E hypothesis was tested with 1037 children. Children were assessed at ages 3, 5, 7, 9, 11, 13, 15, 18, 21 and 26. Participants are divided into 3 groups on the basis of their 5-HTTLPR genotype: s/s homozygotes, s/l heterozygotes and l/l homozygotes. Stressful life events occurring between the 21st and 26th birthdays were assessed using a life-history calendar (a highly reliable method for gathering life-event histories). The 14 events included employment, financial, housing, health, and relationship stressors. 5-HTTLPR genotype did not influence exposure to stressful life events. Participants were assessed for past-year depression at age 26 using a diagnostic interview and observer reports from someone who knows the participants well. Results The effect of life events on self-reports of depression symptoms at age 26 was significantly stronger among individuals carrying an s allele than among l/l homozygotes. Individuals carrying an s allele whose life events occurred after their 21st birthday experienced increases in depressive symptoms from the age of 21 to 26 years. Stressful life events predicted a diagnosis of major depression among carriers of an s allele but not among l/l homozygotes. Life events occurring after the 21st birthdays predicted depression at age 26 among carriers of an s allele who did not have a prior history of depression, but did not predict onset of new depression among l/l homozygotes. Stressful life events predicted suicide ideation or attempt among individuals carrying an s allele but not among l/l homozygotes. The effect of life events on observer reports of depression was stronger among individuals carrying an s allele than among l/l homozygotes. Therefore, the 5-HTT gene interacts with life events to predict depression symptoms, an increase in symptoms, depression diagnoses, new-onset diagnoses, suicidality, and an informant’s report of depressed behavior. It is still possible that individuals have a heritable tendency to enter situations where they encounter stressful life events and the results indicate a gene x gene interaction that was not measured between the 5-HTTLPR and other genes. Psychopathology Page 12 interaction that was not measured between the 5-HTTLPR and other genes. Still, if life events are accounted for just by genetic risk, then they would interact with 5-HTTLPR even if they occurred after the depression episode. The authors tested this by substituting the age-26 measure of depression with depression assessed in a longitudinal study when the participants were 21 and 18 years old, before the occurrence of the measured life events between the ages of 21 and 26. Whereas the 5-HTTLPR x life events interaction predicted depression at the age of 26 years, this same interaction did not post -dict depression reported at age 21 nor at the age of 18 years, indicating that the finding is a true G x E interaction. Consistent with the G x E hypothesis, the relationship between childhood maltreatment and adult depression was significantly moderated by the 5-HTTLPR. Childhood maltreatment predicted adult depression only among people carrying an s allele but not among l/l homozygotes. The effects of psychotherapies for major depression in adults on remission, recovery and improvement: A meta-analysis - Cuijpers (2014) overview of interventions + conclusions about treatment effectiveness only Introduction Several psychotherapies are effective in the treatment of major depression in adults: CBT, behavioral activation therapy, interpersonal psychotherapy, problem- solving therapy, and possibly non-directive counseling and psychodynamic therapies. These therapies result in better acute outcomes when compared to waiting lists, usual care and pill placebo, are equally effe ctive as pharmacotherapies for depression, and the combination of psychotherapy and pharmacotherapy is more effective than either one alone. The authors conduct a meta-analysis of psychological treatments of depression and report their outcomes in absolute (not standardized) terms, including the reduction on scores on commonly used depression measurements, how many people responded and are in remission after treatment, and how many patients do not meet criteria for MDD anymore. Discussion The majority of MDD patients who started with psychotherapy no longer met criteria for MDD after treatment (62%). However, 43% of MDD patients in control conditions also did not meet MDD criteria, and even more in the care -as-usual conditions (48%) => it can be estimated that the added value of psychotherapy is 14% (62%-48%). No significant differences were found between types of psychotherapy, which is in line with other meta-analyses. Here only short-term effects of psychotherapies are investigated. The role of common factors in psychotherapy outcomes - Cuijpers (2019) main message only! No details! Introduction There are 2 positions on why psychotherapies are effective: Due to specific effects, which are realized through the approach of the therapy (e.g. CTs work by changing maladaptive cognitions and BTs work throu gh changing maladaptive behaviors). Due to common/universal/nonspecific factors, which all therapies have in common (e.g. therapeutic alliance, expectations, and a rationale that provides credibility to the treatment being delivered, procedures/rituals provided in a structured manner, a healing setting). Common factors: definitions and models Contextual model - first a therapeutic bond is established and then therapy works through 3 pathways: The therapist-client relationship, which provides the patient with a connection to a caring & empathic person. Patient's expectations/hope - therapy provides explanations of a patient's disorder and ways to cope with it, providing hope that patients are capable of d oing the tasks necessary to complete therapy & solve their problems. Specific therapeutic ingredients that create expectations in patients (activating pathway 2) and produce healthy actions that differ across therapies (these ingredient result in general healthy actions, and the model does not assume that they exert a direct effect by repairing a sp ecific deficit). Psychopathology Page 13 Do all therapies have comparable effects? Similar efficacy of different psychotherapies can be seen as evidence for the dominant role of common factors, but there are many biases and methodologies in research that can also explain this effect (lack of statistical power, low methodological quality, the possibility that different therapies may lead to comparable outcomes vie different mechanistic pathways). On the other hand, common factor models can also explain why there are significant differences between treatment effectivenes s for different psychotherapies in some studies (e.g. researcher allegiance to a specific therapy). Some meta-analyses show that different psychotherapies have comparable effect sizes, but others do not. In sum, meta-analyses of comparative outcome trials partly support the common factors model because some show comparable outcomes for therapies. However, there is insufficient evidence to be sure if all therapies have comparable effects. And, even if all therapies have comparable effects, this cannot be seen as final proof that all therapies work through common factors. Component studies and the common factors model Component studies decompose multicomponent therapies and compare the full therapy with a therapy in which one component is left out or added. The evidence from meta-analyses of these studies is mixed and there are methodological problems that make conclusions unreliable. How can specific and nonspecific factors be examined? There is no straightforward method for examining how therapies work, and most research on specific and common factors has been conducted using correlational studies. There has been little research on temporal associations, dose–response relationships, supportive theoretical frameworks, and laboratory studies. Evidence for selected common factors The therapeutic alliance has 3 components: The bond between the therapist and patient. Agreement about the goals of therapy. Agreement about the tasks of therapy. Stronger alliances are associated with better outcomes, although the magnitude of the relationship is modest, explaining 7.5% of variance in outcomes. While this is quoted as evidence that the therapeutic alliance improves treatment outcomes, the effect is small, most evidenc e is just correlational and causality is far from established. On the basis of several meta-analyses, APA concluded that expressed empathy, the therapeutic alliance and collecting structured client feedback were demonstrably effective elements of the therapeutic relationship across all models of psychotherapy. According to the authors, this is an overly optimistic summary of the literature due to the complexities of explaining how th erapies work. Conclusions Psychotherapy is a complex, multifactorial process, and it is most likely that both common factors and specific factors play a part in the process that leads to recovery, most likely in complicated ways that cannot be captured by simple causal models. Therefore, the only empirical conclusion that can be drawn is that it is not known whether therapies work through common factors, specific factors, or both, and that more and better research is needed to establish this. Ketamine: a paradigm shift for depression research and treatment - Krystal (2019) Psychopathology Page 14 The problem: an overly narrow focus on monoamine signaling The premature conclusion that all antidepressant worked by relieving deficits in monoamine signaling contributed to the failure to identify fundamentally new treatment mechanisms since the discovery of antidepressants in the late 1950s. In the 1990s, limitations of the "monoamine hypothesis of depression" emerged: Monoamine depletion did not reliably induce depression in healthy people, nor did it consistently worsen depression in unmedi cated depressed patients. The opportunity: a broader circuitry perspective A perspective shift suggests that the pathology of depression results from problems in the intrinsic circuitry of the cortex and the limbic system, where neurons are mostly glutamatergic and GABAergic rather than monoaminergic. The authors had previously done research on schizophrenia using the NDMA receptor antagonist ketamine. Considering evidence of cortico-limbic pathology in depression, they decided to test ketamine's antidepressant properties on patients with depression. Left side: historically dominant theory (deficits in serotonin (5-HT) and norepinephrine (NE) based in the midbrain and pons contribute to the biology of depression. Right side: perspective shift (depression as a disorder of cortico- limbic function, in which glutamatergic and GABAergic signaling is also implicated). The results were that ketamine produced rapid, profound and durable antidepressant effects that were dissociated from the initial euphoria normally produced by the drug. Their findings were widely replicated. The replications found that a single dose of ketamine produced antidepressant effects that began with hours, peaked within 24-72h and then dissipated within 2 weeks if ketamine was not readministered. Subsequent studies showed that ketamine was affective in antidepressant non- responders, including bipolar patients. Mechanism of action: Ketamine as "the tip of the iceberg" Paradoxically, ketamine increases neuroplasticity despite blocking NMDA receptors, a critical mediator of plasticity. Some effects may emerge directly as a consequence of NMDA receptor antagonism. These effects are illustrated by blockage of postsynaptic, presumably GluN2B-containing NMDA receptors. When overstimulated, these receptors activate eukaryotic elongation factor-2 (eEF2) and depress BDNF levels. Blockage of these NMDA receptors raises BDNF levels and shuttles AMPA glutamate receptors to the synapse, enhancing synaptic efficacy. Ketamine also may generate its antidepressant effects indirectly by blocking NMDA receptors on GABA interneurons. In this way, ketamine reduces inhibition of glutamate release and, in turn, results in enhanced stimulation of AMPA glutamate receptors. AMPA receptor activation activates a signaling cascade that raises BDNF levels. Local release of BDNF is thought to stimulate TrkB receptors, engaging relevant signaling cascades and resulting in the activation of the molecular target of rapamycin complex 1(mTORC1). This step, in turn, activates local protein synthesis necessary for increasing dendritic spine formation and restoring synaptic connectivity. The convergence of the direct and indirect effects of ketamine on some common mechanisms may constitute elements of a common pathway for antidepressant efficacy, i.e., enhancement of Psychopathology Page 15  constitute elements of a common pathway for antidepressant efficacy, i.e., enhancement of synaptic efficacy and connectivity in key circuits involved in the regulation of mood. It is possible that ketamine effects at sites other than NMDA receptors also contribute to its efficacy as an antidepressant. Ketamine may serve as a prototype for an entirely new class of antidepressant medications, because selectively targeting elements of its effects could preserve efficacy while producing greater tolerability. Changing expectations Ketamine was reserved for patients who failed ECT, but increasingly, it is prescribed to patients who have failed 2 adequate antidepressant treatments. The distinctive rapidity of onset & efficacy of ketamine for the treatment of suicidal ideation raise the possibility that they can be used in urgent care contexts. Psychopathology Page 16