Depression Alternative Treatments

Destroy Depression

Destroy Depression is written by James Gordon, a former sufferer of depression from the United Kingdom who was unhappy with the treatment he was being given by medical personnell to fight his illness. Apparently, he stopped All of his medication one day and began to search for answers on how to cure himself of depression in a 100% natural way. He spent every waking hour researching all he could on the subject, making notes and changing things along the way until he had totally cured his depression. Three years later, he put all of his findings into an eBook and the Destroy Depression System was born. The Destroy Depression System is a comprehensive system that will guide you to overcome your depression and to prevent it from injuring you mentally and physically. More here...

Destroy Depression Summary


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Acute Treatment of Major Depression

The first acute study of IPT was a four-cell, 16-week randomized trial comparing IPT, amitriptyline (AMI), combined IPT and AMI, and a non-scheduled control treatment for 81 outpatients with major depression (DiMascio etal., 1979 Weissman etal., 1979). Amitripty-line more rapidly alleviated symptoms, but at treatment completion there was no significant difference between IPT and AMI in symptom reduction. Each reduced symptoms more efficaciously than the control condition, and combined AMI-IPT was more efficacious than either active monotherapy. One-year follow-up found that many patients remained improved after the brief IPT intervention. Moreover, IPT patients had developed significantly better psychosocial functioning at one year, whether or not they received medication. This effect on social function was not found for AMI alone, nor was it evident for IPT immediately after the 16-week trial (Weissman et al., 1981). The ambitious, multi-site National Institute of Mental Health...

Geriatric Depressed Patients

Interpersonal therapy was initially used as an addition to a pharmacotherapy trial of geriatric patients with major depression to enhance compliance and to provide some treatment for the placebo control group (Rothblum et al., 1982 Sholomskas et al., 1983). Investigators noted that grief and role transition specific to life changes were the prime interpersonal treatment foci. These researchers suggested modifying IPT to include more flexible duration of sessions, more use of practical advice and support (for example, arranging transportation, calling physicians) and recognizing that major role changes (such as divorce at age 75) may be impractical and detrimental. The six-week trial compared standard IPT to nortriptyline in 30 geriatric depressed patients. Results showed some advantages for IPT, largely due to higher attrition from side effects in the medication group (Sloane, Stapes & Schneider, 1985). Reynolds et al. (1999) conducted a three-year maintenance study for geriatric...

Schizophrenia bipolar disorder and major depressive disorder

All three major psychiatric disorders, schizophrenia, bipolar disorder (BP) and major depressive disorder (MDD) affect brain cytoarchitecture. Along with numerous histopathological signals of neuronal malfunction (e.g. reduction in neuronal size, dendritic length and dendritic spines density), these diseases also affect glial cells. There are some indications for loss of astrocytes and GFAP expression in schizophrenia, BP and MDD. In BP and MDD, significant decreases in the numbers and volume of astroglial cells were detected in prefrontal and

Conjoint IPT for Depressed Patients with Marital Disputes IPTCM

It is well established that marital conflict, separation and divorce can precipitate or complicate depressive episodes (Rounsaville et al., 1979). Some clinicians have feared that individual psychotherapy for depressed patients in marital disputes can lead to premature rupture of marriages (Gurman & Kniskern, 1978). To test and address these concerns, Klerman and Weissman developed an IPT manual for conjoint therapy of depressed patients with marital disputes (Klerman & Weissman, 1993). Both spouses participate in all sessions and treatment focuses on the current marital dispute. Eighteen patients with major depression linked to the onset or exacerbation of marital disputes were randomly assigned to 16 weeks of either individual IPT or IPT-CM. Patients in both treatments showed similar improvement in depressive symptoms but patients receiving IPT-CM reported significantly better marital adjustment, marital affection and sexual relations than did individual IPT patients (Foley et...

Clinical Depression

Examination Survey Epidemiologic Follow-Up Study (NHANES I) suggest that females who engaged in little or no recreational physical activity are at a twofold increased risk of developing clinically elevated symptoms of depression over an 8 year follow-up period (OR, 1.9 95 CI, 1.1-3.2) (Farmer et al, 1988). In males, however, physical inactivity predicted depressive symptoms over the follow-up period only if they reported clinically elevated symptoms at the baseline assessment (OR, 12.9 95 CI, 1.798.9). In the Alameda County study, physical inactivity conferred an increased risk for depression in a population sample of non-depressed individuals of both genders (Camacho et al, 1991). Physical activity levels and depressive symptoms were assessed by self-report in 1965, 1974, and 1983. Compared to participants who reported high physical activity levels in 1965, men and women who reported low physical activity levels were at increased risk (males OR, 1.76 95 CI, 1.06-2.92 females OR, 1.70...


Mechanisms (including the administration of common antidepressant medications that modulate synaptic serotonin levels), and western blot analysis, to show that acute increases in serotonin modulate GSK-3P in the mouse brain. Electroconvulsive therapy (ECT) is generally considered the most effective treatment for depression, and although often not as well appreciated, ECT is an efficacious treatment for mania as well 102 . The requirement for anesthesia, repeated visits to the clinic, and public stigma generally limit its use to refractory cases (or situations where pharmacological antidepressants are contraindicated such as pregnancy). Electroconvulsive seizure (ECS), an animal model of ECT, alters phosphorylation of GSK-3. Roh and colleagues found that a single administration of ECS to rats resulted in an increase in brain GSK-3P phosphorylation after 10 minutes 103 . In a follow-up study, this group provided evidence that this phosphorylation may occur in an Akt-dependent manner 104...

Major Depression

Problems with depression and emotional distress are extremely common among HIV-infected patients (283, 286-288), with the prevalence of concurrent major depressive diagnosis between 4 and 10 among patients diagnosed with HIV (289) The lifetime prevalence is estimated to be 22-45 (288, 290-292). A much larger proportion of infected patients have significant depressive symptoms, but have not been formally diagnosed with major depression, with estimates approaching 50 in our clinic. The risk of depression is elevated even among patients at risk for contracting HIV and also among people prior to being diagnosed first (290), and in the early stages of the disease, the prevalence of major depression in HIV-positive patients is similar to that of demographically similar HIV-negative individuals (288, 290, 293). It should be emphasized that people with HIV report a history of depressive symptoms prior to seroconversion (283). This suggests that many people who develop depression after...

Examples Of The Evidence Base

One of the most famous and most expensive therapy outcome studies was the National Institute of Mental Health (NIMH) Treatment of Depression Collaborative Research Program, which will be considered in order to illustrate the problems that have arisen from the general failure to find differential effectiveness of therapy outcome (see Elkin et al., 1989 Elkin, 1994) but also to illustrate other issues about the evidence base. This trial was the largest of its kind ever carried out. There were 28 therapists working at three sites eight therapists were cognitive-behavioural, 10 were interpersonal therapists, and a further 10 psychiatrists managed two pharmacotherapy conditions, one being imipramine plus 'clinical management', the second being placebo plus 'clinical management'. Two-hundred-and-fifty patients meeting the criteria for major depressive disorder were randomly allocated between the four conditions. The therapies were manualised and considerable training and supervision...

Nature And Nurture In Treatment

A nature-based perspective would tend to support providing biological treatment for patients with personality disorders. But the efficacy of drugs has to be proved in clinical trials. Currently, severe personality disorders are often seen by psychiatrists who prescribe pharmacotherapy. In the borderline category, patients are often prescribed as many as four to five drugs (Zanarini, Frankenburg, Khera, & Bleichmar, 2001). Yet the value of pharmacotherapy in this group is not well substantiated. While a number of drugs have been used (Soloff, 2000), the best that can be said for them is that they take the edge off symptoms such as impulsivity (Paris, 2003). Notably, all agents were originally developed for other conditions neuroleptics for schizophrenia, antidepressants for depression, and mood stabilizers for bipolar disorder. When we understand the unique pathophysiology associated with personality traits and disorders, we may be in a better position to develop more specific and...

Rationale for Taking Self Report into Everyday Life

Modern EMA methods have made use of innovations in data-collection technology, but EMA is not primarily a technological development. It more fundamentally addresses the design of data-collection protocols in relation to study objectives. Bolger and colleagues (2003) have enumerated three broad functions of EMA data collection characterizing persons and individual differences (e.g., level of depressive symptoms) estimating within-person variability (e.g., standard deviation of pain intensity levels over a 1 month period) and estimating

Kathryn L Bleiberg and John C Markowitz

Interpersonal psychotherapy (IPT) is a time-limited (12-16 sessions), diagnosis-targeted, empirically tested treatment. Relative to most psychotherapies, it has been carefully studied but, until recently, used primarily in research settings and not widely used in clinical practice. The success of IPT in the treatment of outpatients with major depression has led to its testing for an expanded range of diagnostic indications. Furthermore, it has grown from being a treatment used by research therapists into an increasingly popular treatment approach for clinicians in private practice.

Depressed Adolescents IPTA

Mufson, Moreau & Weissman (1993) modified IPT to address developmental issues of adolescence. In adapting IPT to this population, they added a fifth problem area and potential focus the single parent family. This interpersonal situation appeared frequently in their adolescent treatment population and actually reflected multiple wider social problems in an economically deprived, high crime and drug-filled neighbourhood. Other adaptations included family and school contacts. The researchers completed a controlled 12-week clinical trial comparing IPT-A to clinical monitoring in 48 clinic-referred, 12- to 18-year-old patients who met DSM-III-R criteria for major depressive disorder. Thirty-two patients completed the protocol (21 IPT-A, 11 controls). Patients who received IPT-A reported significantly greater improvement in depressive symptoms and social functioning, including interpersonal functioning and problem-solving skills (Mufson, Weissman & Moreau, 1999). Mufson is completing...

Depressed HIVPositive Patients IPTHIV

Recognizing that medical illness is the kind of serious life event that might lend itself to IPT treatment, Markowitz etal. (1992) modified IPT for depressed HIV patients (IPT-HIV), emphasizing common issues among this population including concerns about illness and death, grief and role transitions. A pilot open trial found that 21 of the 24 depressed patients responded. In a 16-week controlled study, 101 subjects were randomized to IPT-HIV, CBT, supportive psychotherapy (SP), or IMI plus SP (Markowitz et al., 1998). All treatments were associated with symptom reduction but IPT and IMI-SP produced symptomatic and functional improvement significantly greater than CBT or SP. These results recall those of more severely depressed subjects in the NIMH TDCRP study (Elkin et al., 1989). Many HIV-positive patients responding to treatment reported improvement of neurovegetative physical symptoms that they had mistakenly attributed to HIV infection.

Depressed Primary Care Patients

Patients with current major depression (n 276) were randomly assigned to IPT, nortriptyline, or primary care physicians' usual care. They received 16 weekly sessions followed by four monthly sessions of IPT (Schulberg et al, 1996). Depressive symptoms improved more rapidly with IPT or nortriptyline than in usual care. About 70 of treatment completers receiving nortriptyline or IPT recovered after eight months, compared to 20 in usual care. This study had an odd design for treatment in the United States in bringing mental health treatment into medical clinics, but might inform treatment in the United Kingdom, where a greater proportion of antidepressant treatments are delivered in primary care settings.

Antepartum Postpartum Depression

Pregnancy and the postpartum period are times of heightened depressive risk for patients who may wish to avoid pharmacotherapy. Spinelli & Endicott (2003) compared 16 weeks of IPT to a weekly parenting education control programme in a group of 38 antepartum women with major depression. Pregnancy is deemed a role transition that involves the depressed pregnant woman's self-evaluation as a parent, physiological changes of pregnancy, and altered relationships with the spouse or significant other and with other children. 'Complicated pregnancy' has been added as a fifth potential interpersonal problem area. Session timing and duration are adjusted for bed rest, delivery, obstetrical complications, and child care, and postpartum mothers may bring children to sessions. As with depressed HIV-positive patients, therapists use telephone sessions and hospital visits as necessary (Spinelli, 1997). The IPT group showed significantly greater improvement of depression than the parent education...

Subsyndromally Depressed Hospitalized Elderly Patients

Recognizing that subthreshold symptoms for major depression impeded recovery of hospitalized elderly patients, Mossey et al. (1996) conducted a trial using a modification of IPT called interpersonal counselling (IPC) (Klerman et al., 1987). Seventy-six hospitalized patients over age 60 with subsyndromal depression were randomly assigned to either 10 sessions of IPC or usual care (UC). A euthymic, untreated control group was also followed. Three-month assessment showed non-significantly greater improvement in depressive symptoms and on all outcome variables for IPC relative to UC, whereas controls showed mild symptomatic worsening. In the IPC and euthymic control groups, rates of rehospitalization were similar and significantly less than the subsyndromally depressed group receiving usual care. After 6 months the IPC group showed statistically significant improvement in depressive symptoms and self-rated health as compared to the UC group. The investigators felt 10 sessions were not...

Overview of Recent Research

The few studies addressing the overlapping versus independent nature of these associations have produced mixed results. Frasure-Smith and Lesperance (2003) found that symptoms of depression predicted recurrent cardiac events among post-myocardial infarction patients, but anxiety and anger did not. A measure of general negative affectivity identified via factor analysis of the depression, anxiety, and anger scales also predicted cardiac events. When considered simultaneously, depressive symptoms and the negative affectivity factor were both significant predictors. In patients with coronary artery disease, Frasure-Smith and Lesperance (2008) found that diagnosed major depressive disorder (MDD) and generalized anxiety disorder (GAD) were both independent predictors of subsequent cardiac events. Further, co-morbid MDD and GAD did not increase risk beyond either condition occurring in isolation. Although self-reported symptoms of anxiety and depression also predicted coronary events, most...

Empirical Challenges to Conceptual Distinctions

Often equal the correlations between multiple measures of either of these constructs considered alone (i.e., mono-trait correlations). This indicates a troublesome lack of discriminant validity, a key component of construct validity. Multiple studies across a variety of populations and measures suggest that despite their distinct labels, measures of anxiety and depressive symptoms are more accurately interpreted as assessing a single dimension of emotional distress or negative affectivity (Feldman, 1993 Watson, 2009a). This problem has been acknowledged in psychopathology research for many years, but researchers in behavioral medicine often still interpret measures of depressive symptoms or anxiety as if they assessed the specific characteristic indicated by the scale label. Block (1995) refers to this interpretive error as the jangle fallacy in which distinct scale labels are accepted as evidence that distinct constructs are measured, when in fact it is an unrecognized instance of...

Approaches to Confounding and Statistical Control

Variance in a measured variable that is independent of a closely related variable might not reflect the construct of original interest in the way it did before partialling. For example, variance in a measure of anxiety might not reflect the construct of anxiety to the same extent once it is shorn of overlapping variance with depressive symptoms. This is especially true in instances where large correlations between the predictors reflect substantive overlap (Lynam et al, 2006). Given the well-established substantive reasons for overlap among anxiety, depression, and anger described above, as well as among related symptoms, traits, and disorders, the perils of partialling are a serious challenge to valid interpretations of related statistical analyses.

Differential Therapeutics

As a clinician, when might you think of using IPT As a psychiatrist decides which antide-pressant medication to prescribe based on a patient's symptom constellation and research findings, so too should clinicians consider when to use IPT. The research to date supports that IPT works best for depressed patients who face distressing life events ranging from medical illness to job and relationship changes and conflicts. Patients with interpersonal deficits who report no recent life events or changes will probably fare better in CBT. Interpersonal therapy may also work well for patients with anxiety and personality disorders who report recent life events, but research is in these areas, although promising, is still in the early stages. Interpersonal therapy may be a good option for patients who want to augment their medication treatment with psychotherapy given that IPT and pharmacotherapy share the medical model of depressive illness, IPT seems like a good fit, although further research...

Genetic and Physiological Influences

While the examples cited thus far may appear fairly straightforward, it is important to understand that this work has only recently begun, that the mechanisms being studied are far from simple, and that much additional research will be required before the final story has been told. This complexity can be illustrated with a few additional examples. Williams et al (2003) found that CSF 5HIAA levels are associated with 5HTTLPR genotypes, but in ways that vary as a function of both race and sex. In men and whites, the SS genotype is associated with lower CSF 5HIAA levels, but in women and blacks those with the SS genotype have higher 5HIAA levels than carriers of the L allele of both races and sexes. This finding suggests that both race and sex need to be tested in any attempts to relate 5HTTLPR genotypes to phe-notypes whose expression may be influenced by CNS serotonin function. The importance of this approach is illustrated by recent findings in a study by Brummett and colleagues...

Selective Serotonin Reuptake Inhibitors

Results from uncontrolled studies suggest that SSRIs are effective for anxiety in PD (42-44). In an open-label study (n 10), Menza et al. (42) reported that citalopram (mean dose 19mg d) improved anxiety in depressed PD patients. In a study of 30 patients, paroxetine (20 mg twice daily) reduced psychic and somatic anxiety symptoms, as well as depressive symptoms after six weeks (43). Sertraline was also found to have anxiolytic effects in PD patients (44). Although these data are derived from uncontrolled studies, many specialists prefer to use SSRIs for managing anxiety and depression in PD (49).

Detection and Assessment

There are no reliable and empirically derived criteria for recognition of depression in PD. Therefore, it is not surprising that depression remains under-detected and under-treated in the PD population (15,71). In a clinic-based study, nearly two-thirds of patients with clinically significant depressive symptomatology were not receiving antidepressant therapy (11). Older individuals often underreport depressive symptoms and are likely to focus on somatic or vegetative complaints (e.g., fatigue or loss of energy, reduced sexual desire or functioning, pain, sleep changes, or appetite changes), which are the prominent features of mood disorders as well as PD (102). Patients may simply attribute any mood symptoms to their PD, even when their PD has been relatively stable and the mood changes are relatively acute. In one study, over half the patients who had clinically significant depressive symptoms did not consider themselves depressed (11). The DSM-IV diagnostic criteria for major...

Assessment of Efficacy

Overall, based on clinical experience and the available scientific data, SSRIs and TCAs may be considered useful for the treatment of depression in PD, and the agent that provides the best overall clinical benefit-to-risk profile should be selected (168). Amoxapine and lithium should be avoided, given the propensity of these agents to worsen motor symptoms and the availability of safer agents (169,170). Additionally, the nonselective MAO inhibitors (e.g., isocarboxazid, phenelzine, and tranylcypromine) should be avoided in levodopa-treated patients due to the risk of hypertensive crisis. Several antidepressants, such as bupropion, fluoxetine, fluvoxamine, nefa-zodone, and paroxetine, are potent in vivo inhibitors of various cytochrome P450 (CYP450) drug-metabolizing isoenzymes (171,172). These antidepressants may increase the risk for drug interactions. The first step in treating a patient who fails to respond to treatment is to increase the dosage of the antidepressant. If a patient...

Problemsolving Skills Training

This training is a highly useful component in a number of behaviour therapeutic methods across a variety of problem areas. To illustrate, many depressed patients are characterized by deficient problem-solving skills (Nezu, 1987) and there is evidence that problem-solving training contributes to mood improvement among depressives. Problem-solving training is also an important part of communication training among couples with relationship distress (Emmelkamp et al., 1988). Favourable results were also reported when problem-solving training was added to exposure in vivo in the treatment of agoraphobic patients (Kleiner et al., 1987). Likewise, among schizophrenic patients, problem-solving training was shown to be an important supplement to social skills training (Hansen, 1985).

Communication Training

Relationship distress between partners can give rise to a dramatic increase in the risk of clinical depression. About half of the women who are in treatment for depression report marital difficulties. In some cases individual therapy for the depressed patient is inadequate and needs to be supplemented with treatment efforts focused on the relationship issues. Three controlled studies examined the effect of couple's therapy (communication training) on depression (Beach & O'Leary, 1992 Emanuels-Zuurveen & Emmelkamp 1996 Jacobson et al., 1991). There was no overall difference in mood improvement between patients in the individual cognitive behavioural therapy versus those in couple's therapy but relationship improvement was significantly higher among patients in couple's therapy. These findings suggest that depressed patients with marital difficulties are better served by couple's therapy than by individual cognitive behavioural therapy. Moreover, the additional benefit in terms of...

Intervention Research

Given the large body of evidence suggesting that low levels of social integration social support are predictive of cardiovascular disease outcomes, the Enhancing Recovery in Coronary Heart Disease (ENRICHD) trial was designed to provide psychosocial treatment to individuals who had recently suffered an MI and also perceived low social support availability (Berkman et al, 2003). Over 2000 individuals with low levels of perceived social support, high levels of depressive symptoms, or both, were randomized to either usual care (with private physician) or psychosocial treatment, which consisted of both individual cognitive behavioral therapy and group therapy. A tailored therapy program was designed for each participant that addressed social skill deficits, cognitive factors contributing to dissatisfaction with social support in one's network, network development, support needs and preferences, and individual factors (e.g., anxiety) that might be contributing to deficiencies with support...

Mechanisms Linking Social Networks to Health Outcomes

Neuroendocrine responses even in the absence of mobilizing emotional support. For example, in Sheldon Cohen's experiments exposing volunteers to an intranasal dose of the cold virus, individuals reporting high social network diversity (i.e., the presence of social ties in many domains including the work-place, community groups, churches) experienced roughly half the risk of succumbing to a symptomatic cold compared to more isolated individuals, even though the experiments did not involve any manipulation of social support in the laboratory (1997). Presumably, this finding is explained by some as-yet unaccounted for the effect of social network integration on immune functioning (i.e., the ability to fend off the cold virus). Furthermore, longitudinal data from the Framingham Study (Loucks et al, 2006) as well as the MacArthur Successful Aging Study (Loucks et al, 2006) have reported associations between higher levels of social networks and lower levels of inflammatory markers such as...

General Treatment of Psychosis

The management of the psychotic PD patient begins by searching for correctable causes, including infection, metabolic derangements, social stress, and drug toxicity. Infections may not always cause fevers in the geriatric population, so a search for urinary tract infections or pneumonias is warranted. Some PD patients who did not manifest psychotic symptoms at home may decompensate upon moving into the hospital environment. In many of these cases, moving the patient into a secure familiar environment or treating the underlying medical illness may ameliorate psychotic symptoms (19). Finally, medications with CNS effects may cause or exacerbate psychosis in PD and are often overlooked. These medications include pain or sleeping medications such as narcotics, anxiolytics, hypnotics, and antidepressants.

Dean Filandrinos Thomas R Yentsch and Katie L Meyers

John's wort has demonstrated clinical efficacy for mild to moderate depression and compares favorably to other more potent or toxic antidepressants. Low side effects and potential benefits warrant its use as a first-line agent for select patients with mild to moderate depression or anxiety-related conditions. Benefits related to other reported uses such as an antimicrobial, agent to treat neuropathic pain, antiinflammatory, treatment alternative for atopic dermatitis, and antioxidant are either not well documented or evidence is encouraging but not conclusive and further study is needed. St. John's wort has an inherently wide margin of safety when taken by itself, with most reported adverse drug reactions (ADRs) being related to skin reactions. Isolated, but more significant ADRs have been reported in relation to neurological effects, impact on thyroid function, and increased prothrombin time. Of greatest concern is the potential for interactions between St. John's wort and...

Incidence Prevalence and Risk Factors

Incidence rates for PD dementia range from 4 to 11 per year, with a relative risk for the development of dementia in PD of 2 to 6 (12,129,131-133). Age and severity of extrapyramidal symptoms were associated with an overall risk of developing dementia. One study demonstrated that age and severity of disease by themselves were not associated with a greater risk of dementia, but the combination of these two features resulted in an almost 10-fold greater risk (134), suggesting a combined effect. Later age of onset of PD, longer duration of PD symptoms, the presence of hallucinations, depressive symptoms, and a family history of dementia have also been reported to be risk factors for dementia, although less consistently.

Techniques for contrasting experimental conditions

Non-switch difference is larger for one task-type than the other. Factors whose measurements and statistical comparisons are made within subjects, as are those described above, are within-subjects factors, and those whose levels contain data from different individuals (e.g., depressed patients vs. controls) are between-subjects factors. Within-subjects factors generally offer substantially more power and have fewer confounding issues (e.g., differences in brain structure and HRF shapes) than between-subjects factors.

General Treatment of Dementia

And medications with CNS effects (sedatives, narcotics, antidepressants, anxiolytics, and antihistamines) should be discontinued, or used sparingly. The clinician should also be aware that other commonly prescribed medications, including antiemetics, antispasmodics for the bladder, H2 receptor antagonists, antiarrhythmic agents, antihypertensive agents, and nonsteroidal anti-inflammatory agents, may also cause cognitive impairment.

Management of Depressed Mood

Although Dianne's sleeping and eating improved to some extent, her worrying lessened and her panic attack disappeared, Dianne kept on feeling sad and low on energy. Thus, the probable diagnosis of general anxiety disorder was not confirmed however, the diagnosis of depressive disorder was reaffirmed. Therefore after seven sessions of alcohol treatment, the manual Spouse-aided Therapy with Depressive Disorders (Emanuels-Zuurveen & Emmelkamp, 1997) was incorporated into Dianne and Mick's treatment programme. Inactivity being one of Dianne's most salient high-risk situations, we introduced activity training as an intervention to tackle negative mood as well as her drinking problem. Activation training is a fairly common behavioural technique in treating depression, derived from Lewinson's theory of depression. We encouraged Mick to help his wife in organizing her week combining basic daily activities (like getting dressed in the morning), taking care of neglected activities (such as...

Monoamines as Neurotransmitters

Monoamine oxidase (MAO) inhibitors are drugs that block monoamine oxidase, the enzyme in presynaptic endings that breaks down catecholamines and serotonin after they have been taken up from the synaptic cleft. These drugs thus promote transmission at synapses that use monoamines as neurotransmitters. Such drugs have proven useful in the treatment of clinical depression, suggesting that a deficiency in monoamine transmission contributes to that disorder. An MAO inhibitor is also used to treat Parkinson's disease, because it increases the ability of dopamine to function as a neurotransmitter.

Inducible expression of mutant DISC1

We generated a mouse model of conditional and inducible expression of human mutant DISC1 using the Tet-off system (Pletnikov et al., 2008). Mutant DISC1 is a hypothetical protein product of the balanced t(1 11) chromosomal translocation identified in a Scottish pedigree with high load of major mental disorders, including schizophrenia and major depression (Millar et al., 2001 Ishizuka et al., 2006 Chubb et al., 2008). Fine mapping and cloning have identified a disrupted gene on

Summary And Conclusions

Exposure therapies are the treatment of choice in adult specific phobia, social phobia, agoraphobia, and obsessive-compulsive disorder (Emmelkamp, 2004) and have also been found quite effective in phobic children (Nauta et al., 2003). Studies of the behavioural treatment of depression have come to a standstill due to the rise of cognitive therapy in this area but the lack of further research into the behavioural treatment of depression is not justified by the data. There are still a number of important issues that need to be addressed. For example, we have no idea why cognitive therapy, behavioural interventions, IPT and pharmacotherapy work equally well with depressed patients, although various researchers provide various theoretical explanations. Unfortunately, to date there is no evidence that

Rationale for Assessment of Psychosocial Constructs

One issue that has been strongly debated in the literature on psychosocial factors and health is whether assessments include measures of clinical diagnoses (e.g., major depressive disorder, panic disorder) or measures of symptom severity or both. Within the context of studying the health impact of negative emotions and personality, questions have been raised as to whether assessment of symptoms without assessment of clinical conditions is sufficient. An example is the assessment of depressive symptoms versus major depressive disorder (i.e., clinical depression). The initial studies examining whether depression was linked to increased morbidity and mortality were conducted within psychiatric populations, so an early emphasis in the literature was on clinically diagnosed depression. However, because it is uncommon to have time or resources to complete clinical interviews within the context of large, population-based studies, much of the epidemiologic research on the relation of...

Methods of Assessing Psychosocial Factors

Substantial specialized training to administer. The time, training, and costs involved to develop expertise in these interviews, as well as the extra participant burden such time-intensive interviews create, very often make it prohibitive to use such interviews in large, population-based studies, particularly those in which mental health is not a primary focus. The need for less time-consuming measures has prompted the development of self-report questionnaires based on diagnostic interviews. These types of questionnaires increasingly are being used as screening tools for common mental disorders in clinical research and in population-based studies. For example, the Primary Care Evaluation of Mental Disorders (PRIME-MD) (Spitzer et al, 1994) was developed as a clinician-administered interview for use in primary care to diagnose five common disorders based on criteria set forth in the APA's DSM. Subsequently, a self-administered version was developed as the Patient Health Questionnaire...

Future Research Directions

(1) Investigating health-promoting factors. While much of the existing research on race ethnic disparities in health has taken the glass half empty approach, we suggest an expansion in focus to include a complimentary glass half full approach. In other words, future research should investigate factors contributing to better health among various race ethnic groups. Ideally, this approach will lead to greater understanding of factors that preserve and or promote health for specific populations. For example, blacks in the USA have lower lifetime prevalence of major depressive disorders compared to other race ethnic groups (Williams et al, 2007). Future investigations of individual and environmental factors that are protective for black mental health are needed to advance the literature on this topic.

Newer Target Of Lithium Direct And Indirect Inhibition Of Glycogen Synthase Kinase

In 1996 it was discovered that lithium inhibited the enzyme glycogen synthase kinase-3 (GSK-3) 39,40 , a highly conserved protein serine threonine kinase first characterized for its role in glycogen synthesis. These findings raised the possibility that GSK-3 inhibition might play a role in the treatment of bipolar disorder and depression. However, the past two years has seen the emergence of exciting new biochemical, pharmacological, genetic, and rodent behavioral studies, all of which support the hypothesis that inhibition of GSK-3 represents a therapeutically relevant target for lithium's mood stabilizing properties. Furthermore, as we discuss, more recent preclinical evidence implicates the modulation of GSK-3 in either the direct or downstream mechanism of action of many other mood stabilizer and antidepressant medications currently in use (Table 7.1). Antidepressants

Properties as Protein

Since the discovery that MAO inhibitors are antidepressants, large numbers of inhibitors of MAOA and MAOB have been synthesized. The early MAO inhibitors were hydrazine or cyclopropylamine derivatives that showed little selectivity to the two forms of MAO. The acetylenic MAO inhibitors, clogy-line and ( )-deprenyl, however, exhibit a high degree of selectivity to MAOA and MAOB, respectively. They have been found to act as mechanism-based irreversible inhibitors of MAO. These compounds first form a noncovalent complex with the active site of the enzyme, followed by the normal catalytic process to generate a reactive species, which reacts with the enzyme to form an irreversibly inhibited species. Another type of inhibitor is a selectively reversible inhibitor, which can sometimes be derived from the substitution of the hydrogen at a-carbon of MAO substrate by a methyl group. The affinity of MAO to these inhibitors is often higher than it is for its substrates, with a K value of 10 5 to...

Cardiovascular Complications

Chemotherapy, particularly alkylating agents like cyclophosphamide, can induce infertility and, in women, premature menopause, with its attendant problems of hot flashes, mood swings, vaginal dryness, and urinary incontinence. Cyclophosphamide is commonly used in breast cancer, but management of the menopausal symptoms is complicated by the fact that hormone replacement therapy is considered contraindi-cated in patients with a history of breast cancer. Consequently, other treatments must be used for hot flashes, such as antidepressants.52 This example illustrates the importance of both recognizing the symptoms related to ovarian failure in a cancer patient in which it would be otherwise unexpected, and having knowledge of the oncologic considerations of the therapies being chosen.

Gene Stress Interaction Life Events and Other Natural Stressors

Activation or dysregulation of the HPA system is the most frequently invoked mechanism to explain effects of psychological stress on disease, both physical and psychiatric (see Chapter 43). This is undoubtedly due to actions of the glucocorticoid hormone, cortisol, on diverse physiological functions and tissues of the body, including metabolism and activities of the cardiovascular, immune, and central nervous systems. Some HPA phenotypes are also heritable. For instance, genetic variance appears to account for half or more of interindividual variability in basal cortisol levels aggregated across multiple measurements in the morning (Bartels et al, 2003 Meikle et al, 1988) and similar, if somewhat lesser, heritabilities are seen in the cortisol response to morning awakening (Kupper et al, 2005 Wust et al, 2000). With respect to molecular variation, a series of investigations has focused on the corticotropin-releasing hormone type 1 receptor (CRHR1) gene. In the first of these,...

Evidence For Drug Treatments

There is evidence that serotonin reuptake inhibitors (SRIs) are more effective than placebo (Abramowitz, 1997 Goodman et al., 1990 Kobak et al., 1998 Piccinelli et al., 1995) and more effective than other kinds of antidepressants (Hoehn-Saric et al., 2000 Picinelli et al., 1995) in reducing OCD symptoms in clinical trials. The evidence suggests that different serotonin reuptake inhibitors have similar efficacy (Kobak et al., 1998 Picinelli et al., 1995) but clomipramine has a higher rate of adverse effects than selective serotonin reuptake inhibitors (Jenike, 1998). Unfortunately most drug studies assess response only over a short period. One prospective study showed that sertraline produced further significant improvement in a 40-week open label extension of a RCT (Rasmussen et al., 1997). Over 50 of patients respond to serotonin reuptake inhibitors (Erzegovesi et al., 2001 Ravizza et al., 1995) but there is evidence of a rapid return of symptoms in most treatment responders...

The Effect Of Comorbid Depression On Response To Bt Cbt And Sri Treatment

Abramowitz et al. (2000) found that patients with severe depression showed significantly less improvement with CBT, yet even highly depressed patients showed moderate treatment gains. Cox et al. (1993) found that exposure was not significantly effective for depressed mood. Hoehn-Saric (2000) found an SRI (sertraline) was better for co-morbid OCD and major depressive disorder than a non-SRI (desipramine). Hohagen et al. (1998) showed that BT plus fluvoxamine had a significantly better reduction in YBOCS than BT plus placebo in severely depressed patients with OCD.

Difficulties In Assessing Outcome Research

In clinical practice it is rare to meet an individual who only meets ICD-10 DSM-IV criteria for a single personality disorder. As noted above, many individuals meet criteria for more than one personality disorder and others meet criteria for both Axis I and Axis II disorders (Oldham et al., 1995). This makes it difficult to decipher improvements observed clinically or reported in the literature. For example, a person with BPD and major depression may become more impulsive and destructive as the depression lifts (appearing to become more 'borderline') or this behaviour may diminish with the anergia of depression, creating the impression of improved impulse control. Despite the confounding effect of comorbidity when measuring outcome, published studies have generally failed to report this clearly.

Genes and Gene Environment Interactions

One such gene is the serotonin transporter gene, certain alleles of which may predispose to anxiety and or depression (see Chapter 31). People with two copies of the 5-HTTLPR short allele (short short) who have experienced childhood maltreatment are more likely to be diagnosed with major depressive disorders than individuals with one or two copies of the long allele who have experienced similar harsh environments (Caspi et al, 2003 Kaufman et al, 2004). Taylor and colleagues (Taylor et al, 2006c) found that the short allele may function not only as a risk allele for depression in the face of an adverse early environment but as a general sensitivity allele, providing protection from symptoms of depression if the early environment is nurturant. Using a non-clinical sample of 118 adults, we found that people with two copies of the short allele had greater depressive symptomatology if they had experienced early familial adversity compared to people with the short long or long long...

Chronic Negative Affect

Deficits in socioemotional skills may ultimately stabilize into enduring risks for emotional disorders, such as anxiety, depression, and other chronic negative emotional states. These states may act as predisposing factors for adverse physical health outcomes (Hemingway et al, 2003). For example, hostility has been tied to the development of metabolic syndrome among children and adolescents (Dembroski et al, 1985) and to an increased risk for coronary heart disease (CHD) and hypertension (Julkunen et al, 1994). Major depression, depressive symptoms, and history of depression have all been identified as predictors of cardiac events (Frasure-Smith et al, 1995), and depression is a risk factor for mortality following myocardial infarction, independent of cardiac disease severity (Frasure-Smith et al, 1995). State depression, as well as clinical depression, have been related to sustained suppressed immunity (Herbert and Cohen, 1993). Anger appears to play a significant role in the...

Individual Level Child Health Behaviors

With lower education and income (Goodman, 1999 Goodman et al, 2003 Kubik et al, 2003 Mendelson et al, 2008). Depression among adolescents, in turn, is associated with a series of other outcomes. For example, Goodman and Huang (2001) report that depressed adolescents experience fewer routine physical examinations and utilize fewer medical and more mental health resources. Depression has also been linked to adolescent substance use (Kubik et al, 2003) and Goodman and Huang (2002) reported that depressive symptoms may be one mechanism through which SES affects cigarette smoking and cocaine use among adolescents.

Conclusions and Future Research Directions

Our preliminary work on altered allopreg-nanolone reactivity to stress in women with depressive disorders suggests that investigations in the role of neuroactive steroid stress respon-sivity and the regulatory role of such responses with regard to the HPA axis in the pathophys-iology of depressive disorders in humans may be indicated. While this represents an exciting new direction in behavioral medicine for understanding biobehavioral factors in depressive illness, it will be important to proceed cautiously by first establishing reliable studies in healthy human males and females on the time course of neurosteroid responses to stress, as has been done for the HPA axis response to social stress (Kirschbaum et al, 1993). Our prior work suggests that peak allopregnanolone stress levels in human females may occur at a different time point than in rodents.

Information from Human Studies

Wismer Fries et al (2005) reported that children who had lived in orphanages with limited social contact for an average of 17 months before being adopted showed lower overall urinary vasopressin levels for 4 days and lower urinary oxytocin during a game involving lots of mother-child touching compared with age-matched children who had always lived with their parents. Adult men who experienced early parental separation have also failed to show normal inhibition of cortisol following intranasal oxytocin administration (Meinlschmidt and Heim, 2007), while adult women who had experienced childhood abuse or neglect had lower oxytocin levels in their cerebrospinal fluid (Heim et al, 2008). Together, these studies suggest that central oxytocin and vasopressin pathways may show long-term effects of early life events involving parental attachment. In young unmarried adults, higher plasma oxytocin levels were linked to stronger attachment to their parents and to lower...

Estrogen Deprivation Increases Risk for Depression and Medical Illness

While the most common symptoms associated with progressive ovarian failure and estrogen deprivation during the menopause transition are vasomotor (e.g., hot flushes), perimenopausal women are also at increased risk for clinical depression. While most women will not suffer from clinically significant depressive symptoms during the menopausal transition, longitudinal studies in community samples have consistently documented an increased risk for clinically significant depressive symptoms or major depressive episodes during the menopause transition, with odds ratios generally ranging from 1.3 to 4.0 (e.g., Cohen et al, 2006 Freeman et al, 2009). That the fluctuations in hormones during the menopause transition contribute to the development of depression in vulnerable women is supported by the work of Freeman (2006) who showed that greater variability in estra-diol levels, and not the estradiol levels per se, was associated with both higher depressive symptoms and diagnosed major...

Is the Pattern of HAND Changing with Aging

Lastly, it has been shown that psychiatric disorders have a greater prevalence in older HIV-infected individuals as compared to younger HIV-infected individuals. This is the case not only for depressive symptoms, but also alcohol abuse and dependence as well as drug abuse and dependence. While depressive disorders have been demonstrated to be independent from HAND (28, 103), this was shown in relatively young individuals and needs to be fully explored in older individuals. Contemporary nonacute drug use in HIV-infection is known to worsen the overall cognitive deficits (104), but the chronic effects of such drugs are less clear (105). It has been shown that lower socio-economic status in HIV+ drug users had more influence on neuropsychological performance than the drug use status per se (106).

Project Title Mentored Patient Oriented Research Career Development Aw

Summary PROPOSAL (Adapted from the applicant's abstract) Major depression is a significant independent risk factor for the development of ischemic heart disease and is a potentially lethal comorbid condition in post-myocardial infarction patients. The pathophysiology that links major depression to the occurrence of heart disease is not known. Preliminary observations indicate that platelet reactivity is increased in depression, which implies that depressed patients may be prone to thrombus formation, hence at increased risk for catastrophic cardiac events. There are considerable data indicating that the serotonergic system is altered in depression, both in the central nervous system (CNS) and in the platelets. In the periphery, the most notable and consistently replicated observation of serotonergic alteration is an increased B max for the serotonin-2A (5-HT2A) receptor on the platelets of depressed individuals. The platelet 5-HT2A receptor plays a central role in platelet reactivity...

Mortality and Morbidity

Various other chapters in this book report on evidence that social, psychological, and lifestyle factors impact on overall health outcomes. Also, meta-analyses and systematic reviews suggest that lack of social support (Lett et al, 2005), depressive symptoms (Nicholson et al, 2006), and unhealthy lifestyle behaviors such as lack of physical exercise (Oguma et al, 2002) are associated with increased risk of developing cardiovascular disease and all-cause mortality. Although these reviews do not explicitly distinguish between studies using middle-aged and older populations, it is good to realize that in fact the majority of meta-analyzed studies examining the impact of behavioral factors on general health outcomes have been conducted among older persons, simply because morbidity and mortality most commonly occur in the oldest age groups. Therefore, there is no doubt that these behavioral factors continue to impact on general health outcomes such as mortality and (cardiovascular)...

Aging Related Outcome Frailty

In addition, various cross-sectional reports have linked depressive symptoms to aspects of frailty. However, cross-sectional associations are hard to interpret since frailty status itself could result in increased feelings of depression and mood changes. For certain aspects of the frailty syndrome, longitudinal associations with depression have been confirmed as well. Persons with high depressive symptoms have shown a larger 4-year decline in walking speed (Penninx et al, 1998) and a larger decline in muscle strength (Rantanen et al, 2000). In addition to negative emotions, Ostir and colleagues (2004) found that positive affect could significantly reduce the onset of frailty, which adds to a growing positive psychology literature showing that positive affect is protective against the functional and physical decline associated with frailty (see Chapter 14).

Aging Related Outcome Cognitive Impairment

Various studies have also linked unfavorable psychological and social factors to a more rapid cognitive decline. Depressive symptoms, for instance, have been found to speed up cognitive decline over time (Yaffe et al, 1999). Interpretation of such observations is not easy, since it could be that depressive symptoms impact on cognitive function through underlying physiological effects, or it could simply be that depressive symptoms pick up some early signs of deteriorating cognition and therefore are rather markers of an early stage of cognitive decline. Furthermore, widowhood has been shown to be associated with greater cognitive decline in older adults (Aartsen et al, 2005), which could partly be due to underlying loneliness, also shown to be linked with a more rapid cognitive decline and a doubled risk for Alzheimer's disease (Wilson et al, 2007).

Biological Indicators of Health or Resistance to Disease

CHD, and depression (Dekker et al, 2008 Herbert et al, 2006 Raison et al, 2006). Cortisol also contributes to memory function across the life span, with evidence that long-term exposure to high levels of glucocorticoids is associated with memory impairments and reduced hippocampal volume in the aging brain (Lupien et al, 2005). Until the advent of salivary assays, cortisol was primarily measured in blood or urine. Since cortisol secretion has a pronounced diurnal rhythm, this resulted in difficulty in accurately capturing representative cortisol levels in population studies, as the timing of data collection required standardization. Nevertheless, two studies showed that a single sample recorded early in the day was predictive of future clinical depression in adolescents or adults at high risk (Goodyer et al, 2000 Harris et al, 2000). A high cortisol testosterone ratio was found to predict incident CHD in a longitudinal study in South Wales, UK, probably through influences on the...

Behavioral analysis of DISC1 mouse models Table

How to differentiate between tests relevant to negative symptoms and tests relevant to depression. Since DISC1 is a candidate gene not only for SZ, but also for other mental disorders including depression, such phenotypes are of interest even if not clearly attributed to a specific disease. Social withdrawal can be modeled by a three-chamber sociability test. It has been applied to the Q31L and L100P point mutants (Clapcote et al., 2007) and to the inducible CaMK-Ac Tg (Li et al., 2007) and showed abnormalities in all of them, except for L100P. The constitutive (Hikida et al., 2007) and inducible CaMK-AC Tg (Pletnikov et al., 2008) were tested in other social tests, in which only the inducible CaMK-AC Tg males differed from the wild-type littermates. Anhedonia can be manifested in mice by decreased reinforcing properties of rewards (Nestler et al., 2002). The Q31L, but not the L100P mutants consume less sucrose in the sucrose consumption test. The forced swim test is widely used to...

Prevalence Of Latelife Depression And Anxiety

The Epidemiological Catchment Area Study (ECA) (Regier et al., 1988) was a major study investigating rates of depression and anxiety in the community carried out across five sites in the US. The ECA prevalence rates of major depressive disorder amongst older adults were lower than for younger adults (for review see Powers et al., 2002). In the UK, Lindesay, Brigs & Murphy (1989) reported prevalence rates of 4.3 for severe depression and 13.5 for mild moderate depression in a community dwelling urban sample. Beekman, Copeland & Prince (1999) carried out a systematic review of community-based studies examining prevalence of depression in older adults. Overall, Beekman, Copeland & Prince (1999) calculated prevalence rates of 13.5 for clinically relevant depression but concluded that major depression is relatively rare in later life (1.8 ) whereas minor depression is relatively more common (9.8 ). Similar figures reported by Copeland et al. (1987) and Livingston et al. (1990)...

Upper Airway Colonization

Colonization of the upper respiratory tract by both Gram-negative (GNB Enterobacteriaceae, P. aeruginosa) and Gram-positive bacteria (S. aureus) is more prevalent in the elderly and is related more to the severity of systemic illness and level of care than to age per se (Johanson et al., 1969 Valenti et al., 1978). Factors leading to colonization of the lower and upper respiratory tract include antibiotic therapy, endotracheal intubation, smoking, malnutrition, surgery, and any serious medical illness. Decreased salivation such as that induced by antidepressants, antiparkinsonian medications, diuretics, antihypertensives, and antihistamines also contributes to oropharyngeal GNB colonization.

Evidencebased Psychotherapy With Older People

Scogin & McElreath (1994) produced the first meta-analysis of the efficacy for psychosocial treatments in late-life depression. Scogin & McElreath (1994) included 17 studies published from 1975 to 1990. In their analyses they reported mean effect sizes for treatment versus no treatment or placebo of 0.78, similar to effect sizes of 0.73 reported by Robinson et al. (1990) in their review of psychotherapy for depression across all age ranges. Scogin & McElreath (1994) also carried out separate analyses using a subset of studies satisfying diagnostic criteria for major depressive disorder and reported an effect size of 0.76. They also calculated a mean effect size of 0.3 when comparing cognitive and behavioural therapies with other psychosocial treatments. They investigated treatment delivery methods and reported a mean effect size of 0.74 for group treatments and a mean effect size of 0.77 for individual treatments. Despite the clear superiority of psychological treatments...

Conclusions And Summary

Psychological treatments constitute a much-needed effective treatment alternative to physical treatments for late-life anxiety and depression because many older adults are unable to tolerate antidepressants or there may contra-indications to their use with older people with cardiac problems (Orrell et al., 1995) and in the case of anxiety disorders there may be a number of concerns about the prescription of benzodiazepines (Gerson et al., 1999). Future research is required into the effectiveness of psychological treatment for depression and anxiety in common medical conditions such as dementia, post-stroke depression and Parkinson's disease. A number of studies are currently at early stages of evaluation of efficacy in terms of psychological and physical treatments for depression and anxiety. At present a lot remains unknown about the potential for psychological therapies in a range of settings such as in nursing homes.

Circadian Dysfunction Is a Hallmark of Many Physical and Neural Disorders

In addition to the physical effects resulting from circadian dysfunction, numerous psychiatric illnesses have circadian components. Depression is an interesting case study of a syndrome that presents with both circadian and HPA dysfunction symptomatology. Depressive disorders are characterized by multiple physiological and psychological symptoms. One of the most common physiological observations is disrupted circadian timing, which can manifest as changes in sleep wake cycles (Turek, 2007 Van Cauter and Turek, 1986) and a blunting of the daily rhythm of glucocorticoids (Deuschle et al, 1997). Circadian disruption is a characteristic of depression (Wirz-Justice, 2006), and shift workers often suffer from mood disturbances and an increased risk for depression. In addition, seasonal affective disorder (SAD) reflects dysfunctions in the circadian rhythms (Magnusson and Boivin, 2003). Thus, circadian disruption may be a consequence of experiences that lead to depression, and inability to...

The HPA Axis Under Challenge

Including psychological stress protocols (e.g., cognitive tasks or public speaking paradigms (for an overview, see Kudielka et al, 2009) and a wide variety of pharmacological provocations, physical exercise, or intake of standardized meals. While psychological stressors are central stimuli that are processed at higher brain levels, pharmacological challenge tests are specifically tailored to act at certain levels of the HPA system and operate in a dose-dependent manner. The HPA axis is regulated by the negative feedback action of cortisol on receptors in the hippocampus, hypothalamus. and pituitary gland. The dexamethasone suppression test is used to test HPA axis negative feedback efficiency by determining the degree to which endogenous cortisol release is suppressed by intake of oral dexamethasone. This synthetic glucocorti-coid acts primarily by binding to glucocorticoid receptors in the pituitary gland, mimicking the negative feedback effects of endogenous cortisol such that ACTH...

Hypothalamic PituitaryThyroid Axis

In critically ill patients, the low T3 syndrome has been considered a predictor for mortality (Chopra, 1997). In patients with anorexia nervosa, the low T3 syndrome as well as a smaller volume of the thyroid gland has been observed, which are both reversible after weight gain (Munoz and Argente, 2002). In PTSD and major depression, both hyper- and hypoactivity of the hypothalamic-pituitary-thyroid axis have been described (Boscarino, 2004 Newport and Nemeroff, 2000).

Neurobehavioral Changes

In addition to cognitive changes in diabetes, affective disorders, notably the incidence of depression, is increased in diabetes (Gavard et al., 1993 Lustman et al., 1986). Major depression has a higher recurrence rate, and depressive episodes may last longer in individuals with type 1 or type 2 diabetes (Lustman et al., 1986 Ryan, 1988). A significant relationship between poor glycemic control and major depression has been reported, although this relationship was not supported by other studies. Insulin resistance has been postulated as the missing link between the affective disorders and AD. However there is no conclusive empirical data to support this hypothesis at this time (Rasgon and Jarvik, 2004). It is not clear whether the high prevalence of depression in diabetes is the result of neurobiochemical changes associated with diabetes, or is secondary to psychological factors related to chronic disease state or its treatment.

Assessment And Intervention

He notes that this approach can help alleviate anxiety but he concurs with Parkes that there are more effective ways of managing depressive symptoms such as a goal-oriented approach. This is supported by an earlier paper by Sireling et al. (1988), which used a guided mourning intervention. One group was told to focus on bereavement cues and the second group to avoid them but both groups were encouraged to engage in enjoyable activities and advised about resuming social relationships. Both groups experienced similar levels of improvement in depressive mood. Kavanagh argues that the Lazarus & Folkman (1984) model of stress and coping skills offers a constructive way forward for people experiencing problems in their bereavement. A situation is perceived to be stressful if the repertoire of coping strategies is judged to be inadequate to the challenge. If support is given to develop and extend coping skills, depending on individual need, then the situation will be...

Clinical manifestation

Symptoms are occasionally noted earlier by relatives than by the patient himself. This is why a history given by these persons is of utmost importance. Typical complaints are slowing of reasoning, forgetfulness, difficulties concentrating, lack of energy drive, mild depressive symptoms and emotional blunting. For symptoms and signs see Tables 1 and 2. Emotional Loss of drive and initiative, withdrawal from social activities, failure to manage the financial and administrative aspects of one's life. Depressive mood, emotional blunting

Depression in Older Patients

Major depressive disorder is frequently undiagnosed and untreated in older patients, and can be associated with high morbidity and mortality in this patient group, who are particularly prone to completed suicide or self-neglect. Grief, pain, sleep issues, concurrent medications, altered physiology, and the presence of comorbid medical and psychiatric conditions can complicate the management of depression in older patients. Comorbid medical conditions, including cardiovascular events, stroke, vascular dementia, and Alzheimer's disease, which are common among older patients, can have a significant impact on depression, and vice versa. Depression is not a natural part of the aging process, and it should be diagnosed and actively treated in the elderly, just as it is in younger patients. Pharmacother-apy can be safe and effective in this population, as long as pharmacokinetic and pharmacodynamic properties, as well as the inherent biological differences in the elderly population are...

Etiology and Pathogenesis

The relationship between depression and cardiovascular disorders also provides insight into the mechanisms of depression. Abnormalities in neurotransmitters (including serotonin), platelet-activating factor, and nitric oxide, which are involved in atherosclerotic processes, have been implicated in the pathogenesis of depression (Plante, 2005). Moreover, vascular consequences of depression such as heart rate and pulse pressure variations may lead to endothelial dysfunction in critical microcirculation networks (cerebral, myocardial, and renal) and initiate physicochemical alterations in interstitial compartments adjacent to vital organs. Worsening depressive symptoms after a coronary event were associated with impaired autonomic control of the heart, and mortality was almost three times higher among the patients with MDD at the time of the initial event compared to those without depression (de Guevara et al., 2004). The finding of higher rates of relapse of depression among patients...

Pharmacokinetic And Pharmacodynamic Considerations

The use of antidepressants in older patients can be complicated by several factors. Older individuals use multiple medications (two or more prescription drugs) three times more frequently than younger persons, increasing the potential for interactions. Age-related alterations in physiology can result in variable plasma drug concentrations, which may increase the number of adverse events, and the elderly may be more sensitive to adverse events (McDonald et al., 2002). Aging is associated with a number of neuroendocrine changes, including alterations in monoamine oxidases, noradrenergic neurons, dopaminergic neurons and concentrations, cholinergic neurons and receptors, adrenocorticotropic hormone (ACTH) concentration and function, and serotonin receptors and concentrations (Rehman et al., Recommended initial doses are lower for the elderly for all antidepressants, and increases should be slow and individualized (De Vane et al., 1999). The pharmacoki-netics of some selective serotonin...

Relationship to Behavioural and Neural Functioning

As for FA, MTR is a non-specific marker of neural damage, such as demyelina-tion. Many of the published MT studies have focused on patients with multiple sclerosis, who show decreased MT in both ROI and whole-brain histogram analyses. In other diseases, results are similar, indicating MTR is a viable marker for affected white and gray matter. MTR has been shown to increase with brain development during the first several years of life (Rademacher et al. 1999 van Buchem et al. 2001) and regional decreases with aging have been found (Armstrong et al. 2004). Differences in MTR were sufficiently large to distinguish patients with mild cognitive impairment from patients with Alzheimer's disease and controls (Kabani et al. 2002a Kabani et al. 2002b). A number of published studies have also used magnetization transfer methods to compare the brains in patients with schizophrenia against healthy control subjects (Foong et al. 2001 Bagary et al. 2003 Kiefer et al. 2004 Kubicki et al. 2005)....

Organ Systems Affected By Low T Levels

It is estimated that two million older Americans are depressed (NIMH, 2003). Depression increases with aging, in part due to diseases associated with aging. Although depression is not a part of the aging process, medical diseases associated with aging such as stroke, diabetes, and heart disease reduce physical activity and contribute to depression. It is estimated that 80 of older adults with depression improve when they receive therapy with an antidepressant medication, psychotherapy, or both (NIMH, 2003). T may have a beneficial effect on mood and depression, as it is known to modulate the serotonin and dopamine pathways.

Studies Of Psychological Treatments In Bipolar Disorders

The IPSRT intervention was one of the first systematic psychological therapies developed specifically for individuals with BP. A randomized treatment trial with a two-year follow-up is under way. Interim reports are available on 82 participants initially allocated to IPSRT or intensive clinical management. The trial has two phases - an acute treatment phase and a maintenance phase - and 50 of participants in each group remain in the same treatment arm throughout the study while the remaining participants cross over to the other treatment arm (Frank et al., 1999). The key findings so far are that IPSRT does induce more stable social rhythms (Frank et al., 1994). There were no statistically significant between-treatment differences in time to remission but those entering the trial in a major depressive episode showed a significantly shorter time to recovery with IPSRT compared to intensive clinical management (21 weeks versus 40 weeks) (Hlastala et al., 1997). Interestingly, those...

Therapy for sexual dysfunction General overview

Apomorphine is a centrally effective dopamine receptor agonist. It is less effective and so less important in the treatment of ED, but should be considered in patients with contraindications to PDE-5 inhibitors (APO-go ampullae, max. 100 mg s.c.). Apomorphine seems to be particularly helpful in psychogenic ED and light organic ED. Miscellaneous herbal substances (Yohimbine, Maca, Turnera diffusa) might have a positive effect on sexual function. However, systematic studies have not been performed. These substances have few side effects, but monitoring for possible interactions with HAART is advisable. For psychosocial problems, relationship conflicts or depressive disorders, psychotherapeutic support and if necessary a sexual-medical discussion are advised.

Cognitive and Psychiatric Disturbances

Earlier literature described euphoria as a feature of MS (120). However, depression is now recognized much more commonly, with 50 or more of patients experiencing this affective disturbance in some form during the course of the illness (121-123). Although this is usually relatively mild, major depression can occur (123). Suicide may be a major cause of mortality, accounting for 15 of adult deaths in one series (124). Recently, Feinstein (125) identified warning signs that include living alone, having a family history of mental illness, and reporting social isolation. Patients with a prior history of major depression, anxiety disorder, or alcohol abuse are also particularly vulnerable. The so-called euphoria is actually the inability to inhibit emotional expression, resulting in inappropriate laughing and crying. This occurs with subcortical forebrain lesions (126). Other instances of apparent euphoria seem to be associated with evidence of significant cognitive decline. Euphoria is...

Interpersonal Psychotherapy Rationale

Interpersonal therapy provides a pragmatic, time-limited and interpersonally focused approach to the treatment of major depression. It is modest in its use of psychotherapy jargon and promotes attention to the relationship-based issues that are central to the experience of many depressed patients. The treatment does not become entangled in questions of causation, acknowledging the capacity for depression to both precipitate and reflect interpersonal change, difficulty and loss. Instead it attends to difficulties arising in the daily experience of maintaining relationships and resolving difficulties while depressed. The fundamental clinical task of IPT is to help patients to learn to understand their depressive symptoms in an interpersonal context, and to work towards resolution of interpersonal difficulties such that they will no longer precipitate or sustain the depressive state and so facilitate more effective symptom management. The National Institute of Mental Health (NIMH)...

Overview of Brain Changes inMDD

The cognitive model of depression (Beck, 1961) posits that stressful life events activate cognitive vulnerability and the depressive state develops, resulting in the depressive phenotype that is characterized by increased negative emotion processing (i.e., negative bias) and impaired emotional control (e.g., emotional responses that are too intense or prolonged). Extensive behavioral evidence supports this model, revealing that depressed individuals (1) focus more on negative stimuli and less on positive stimuli (Mogg et al, 1995 Scher et al, 2005), (2) are less easily distracted from negative emotion processing (Ellenbogen et al, 2002 Lyubomirsky et al, 1998 Siegle et al, 2002 Wenzlaff and Bates, 1998), (3) show heightened stress hormone levels such as cortisol that may have deleterious effects on the brain (Sapolsky, 2000), and (4)

Structural Brain Changes in MDD

As we review below, a variety of structural changes have been observed in patients with MDD. These are significant in at least two major respects. First, structural brain differences between patients and controls are suggestive of either a factor predisposing to the development of the disorder or a consequence of the disorder or its treatment. Second, structural brain changes must be taken into account when comparing functional brain activity in patients and controls. For example, functional brain activity in ventromedial PFC reveals decreased activity in MDD patients compared to controls in unadjusted comparisons, but when structural volume loss in this area in depressed patients is taken into account, activity in ventromedial PFC is actually hyperactive in depression (Drevets et al, 1997). Recent reviews (Konarski et al, 2008 Lorenzetti et al, 2009) describe the volumetric changes associated with major affective disorders. Studies investigating...

Functional Brain Changes in MDD

Recent fMRI research reveals that unmedicated individuals with current MDD show hyperactivity of the anterior insula during emotional tasks (Grimm et al, 2008), and that pretreatment activation in anterior insula predicts antidepressant treatment response (Langenecker et al, 2007). In accordance with the cognitive model, depressive symptoms often result from excessive focus and worry about anticipated events that may or may not come to fruition. Based on this evidence, a recent study used a pain processing task during fMRI to examine the neurobiological basis of pain anticipation in MDD (Strigo et al, 2008b). In that study, MDD was associated with increased activation in the amygdala, insula, and ACC during pain anticipation, suggesting that MDD individuals experience increased affective processing even before they actually experience pain. Additionally, greater right amygdala activation during pain anticipation was associated with greater levels of perceived...

Cognitive Behavioural Therapy Rationale

Such findings do not argue against CBT as a treatment for depression. On the contrary they demonstrate its consistently robust performance in the face of many comparative evaluations. However they highlight the relative absence of studies with depressed patients in which CBT was found to be superior to an alternative psychological treatment, a superiority tacit in the predominance of this model of practice. Cognitive behavioural therapy has demonstrated equivalence in good quality pharmacology studies (De Rubeis et al., 1999 Hollon et al., 1992 McKnight, Nelson-Gray & Barnhill, 1992). Hollon et al. (1992) also found no difference in CBT outcome with more severely depressed patients, in contrast to the findings of the TDCRP (Elkin et al. 1995). De Rubeis et al. (1999) also conducted a meta-analysis of four studies comparing CBT and medication for patients with severe depression. Direct comparisons between the two lines of intervention showed no significant differences but overall...

Changes in Brain Function due to Antidepressant Treatment

Importantly, antidepressant medication and psychotherapy may affect different neural nodes in unique ways that are consistent with the cognitive model of depression. These findings add a neuroanatomical perspective to the robust observation that the combination of antidepressant medication and psychotherapy is more effective in the treatment of depression than either treatment alone (Pampallona et al, 2004). In one study (Kennedy et al, 2007), response to venlafaxine relative to response to cognitive behavior therapy was associated with larger decreases in subgenual ACC activity, consistent with the notion that antidepressant medications may primarily affect the regions of the cortico-limbic network that are involved in automatic emotional responses. This evidence is reinforced by studies in healthy volunteers, which indicate that depletion of tryptophan, a precursor to serotonin, is associated with increased amygdala responses to fearful stimuli (van der Veen et al, 2007)....

Brain Based Treatments of Depression

A landmark advance in psychiatry occurred in 2005 when it was demonstrated that deep brain stimulation of subgenual ACC was an effective treatment for depression (Mayberg et al, 2005). The decision to stimulate this brain structure was based on a network analysis of functional changes in the brain in depression and a determination of which loci were most important. In the largest study to date, 20 patients with treatment-resistant depression received sub-genual ACC deep brain stimulation and were assessed at multiple time points before and after deep brain stimulation (Lozano et al, 2008). Additionally, PET was used to measure changes in brain metabolism associated with the antidepressant response to deep brain stimulation. Significant reductions in depressive symptoms were observed 1 week after deep brain stimulation, and a progressive increase in the proportion of treatment-resistant depression patients that showed a clinically significant reduction in depressive symptoms increased...

Problemsolving Therapy Rationale

Research evaluations of problem-solving therapy have been exclusively conducted in primary care and community samples, with patients with mild depressive symptoms. Dowrick et al. (2000), Nezu et al. (1986), and Nezu, Nezu & Perri (1989) have shown problemsolving therapy to achieve greater symptom reduction than no-treatment control conditions for depressed patients at the end of treatment. Nezu's studies reported better outcome for full problem-solving therapy over components of the therapy and this was maintained over a six-month follow up. Dowrick's community sample did not maintain the initial gains over a naturalistic 12-month follow up.

Behaviour Therapy Rationale

Behaviour therapies for depression are underpinned by learning theory as a means of explaining the decline into and resolution of the depressive state and are primarily aimed at engaging or re-engaging the patient in pleasurable and consequently positively reinforcing behaviours. Relative to psychotherapy, behaviour therapy concentrates more on behaviour itself and less on a presumed underlying cause. The basic premise of behavioural treatments is that depression is a learned response in light of low rates of positively reinforcing behaviours and insufficient positive reward from routine behaviour. The aim therefore is to increase the reward experience through behavioural activation. Interventions combine skills based learning such as relaxation skills and problems solving with distress tolerance for negative emotions. As with other models of therapy for depression, behaviour therapy has also been employed as a couples therapy. When compared with individual CBT (Jacobson et al., 1991)...

Human Immunodeficiency Virus and Lupus

In comparison to HIV-positive non-symptomatic patients or control participants, show increased power in the alpha and theta wave bands after controlling for the effects of antiretroviral medication, this association appeared to persist mainly among untreated patients (Baldeweg and Gruzelier, 1997). Furthermore, while increased alpha wave amplitude in HIV-positive symptomatic patients was associated with increased rates of depressive symptoms, decreased alpha wave amplitude in HIV-positive asymptomatic patients was associated with increased rates of depressive symptoms. These results show a sensitivity of EEG waves to the disease and treatment but the authors offer little interpretation of shifts in both lower and higher frequency bands. Other work has inferred cognitive state from ERP observed in the oddball paradigm. Chao and colleagues (Chao et al, 2004) found that HIVpositive individuals had decreased P200 and 300 amplitudes and longer P300 latencies than controls. Moreover, among...

Project Title Safety And Efficacy Of Sertraline For Depression Chf

One leading source of heart failure is ischemic heart disease. Despite knowledge that depressive disorders lead to increased morbidity, mortality and poorer outcomes in ischemic heart disease, little is currently known about the association of CHF and depression. There is evidence that the rate of depression may be high in the CHF population, but no studies have addressed the impact on morbidity and mortality in CHF patients when depression is adequately treated. Funding is requested for a two site, prospective placebo treatment of patients with congestive heart failure and clinically diagnosed major depression. Patients will be enrolled in this study with clinically diagnosed heart failure of NYHA functional > II. Patients will be interviewed and evaluated for major depression by use of the protocol developed by the NIMH-supported Duke Center for the Study of Depression in the Elderly. This includes sections that assess depressive symptoms,...

When Treatment Choice Moderates Event Change on Outcome

For example, in an RCT comparing two treatments of major depressive disorder, it may be that some patients during treatment experience the death of a loved one or another such traumatic life event. Random treatment assignment is unlikely to affect the occurrence of such a traumatic life event. However, it may be that one of the treatments fosters better coping with that life event, resulting in a much better outcome for those affected in that treatment group. This would result in an interaction between treatment choice and the life event on outcome. Since the effect of the life event on outcome depends on the earlier treatment choice, here treatment choice moderates the effect of the life event on outcome, not vice versa.

Psychiatric Comorbidity in HIV

It is well recognized that certain comorbidities common among people infected with HIV affect neurocognitive and functional status in their own right, perhaps in part by reducing cognitive reserve. That HIV and psychiatric comorbidity often interact to affect behavior has made this an important area of investigation (278). Among the most significant psychiatric comorbidities among HIV-infected patients are substance abuse and major depression.

Psychiatric Diseases And Symptoms

Depressive symptoms are common in patients with AD, and in elderly persons with depression it is often difficult to distinguish this from AD. The sleep pattern Sleep problems are common in elderly persons with depressive disorders, and in the Diagnostic Statistical Manual (DSM-IV) of Mental Disorders, sleep deterioration is included as one of the nine criteria for the diagnosis of major depression (American Psychiatric Association 2000). Depression is a fairly common condition. In a recent questionnaire survey in northern Sweden among men and women of ages 18 years and older, the prevalence of major depression was found to be 4.8 in men and 6.3 in women with only minor difference with respect to age (Asplund et al., 2004). In persons with depression, sleep problems occur most frequently during acute depressive episodes, but the disturbed sleep often persists during remission. The sleep symptoms consist mainly of an increase in sleep latency, a reduced total sleep time, and a decrease...

Interactions of HIV and Depression

HIV and major depressive disorder (MDD) may interact in important ways to affect disease progression (303-306). At a behavioral level, depressed patients have greater problems adhering to treatments (307-315). Poor treatment adherence has important implications, as beneficial effects from HAART appear dependent on sustained viral suppression and good clinical outcome (316-321). Failure to maintain adherence increases the possibility of treatment resistance and increased disease burden. Overall, there is considerable evidence that depression and psychosocial stress affect HIV-associated mortality and morbidity (354). There is evidence that this association continues even in the HAART era (355), particularly with advanced age (356-358). On the other hand there is also evidence that the rates of depression are declining as a function of the availability of more effective treatments (358). Findings are mixed with respect to the association between depression and neurocognitive function in...

Gaps In The Evidence Base

Of major concern is the limited number of therapists who can recognize and effectively treat social anxiety disorder. Clinicians are most likely to recognize and diagnose a psychological problem in socially anxious persons who present with a comorbid condition -typically major depressive disorder or alcoholism - and are most likely to treat the comorbid condition before the social anxiety (Ballenger et al., 1998). In addition, studies have reported that, among the anxiety disorders, the most highly utilized psychosocial treatments are dynamic psychotherapy (Goisman, Warshaw & Keller, 1999) and supportive therapy (Rowa et al., 2000). There appears to be an underutilization of efficacious treatments in favour of those that have been less well studied. One promising study demonstrated that general practitioners may be trained successfully to provide brief exposure therapy (eight sessions of 15 to 20 minutes' duration) within a primary-care setting (Blomhoff et al., 2001 Haug et al.,...

Interpersonal Reconstructive Therapy Methods

Elicit detail about input, response, impact on self The IRT case formulation method shows how symptoms and problem behaviors are related to the impacts of earlier important interpersonal relationships, now translated into intrapsychic events involving IPIRs. Marianne's self-talk during her severe depressive episode made the connection between her interpersonal and intrapsychic experiences very clear. The boundary between interpersonal and intrapsychic typically is fluid. Although originally interpersonal, relationships with IPIRs have become internal events. It often does not matter much whether the person who originally provided the template for the IPIR is still living and in the person's life. Internal templates have weak time frames then is now and now is then.

Genetic epidemiology Affective disorders

There is no doubt that affective disorders tend to run in families. Among the first to remark on this was Kraepelin (1921), the founder of modern psychiatric classification, who noted that ''hereditary taint'' was apparent in 80 of his patients suffering from manic-depressive illness. The first studies to distinguish between UPD and BPD were comparatively recent. They were carried out by Angst (1966), a Swiss psychiatrist, and independently, in the same year, by Perris (1966) in Sweden. Perris found that there was a striking degree of homotypia, that is, a tendency for relatives of UP and BP probands to ''breed true'' and exhibit the same type of disorder. However, the findings of Angst were more complex. Among the relatives of probands with UPD there was an increase only of UPD, but among the relatives of BPD probands there was an excess of both UPD and BPD. Most subsequent studies have conformed to the pattern found by Angst (McGuffin and Katz, 1986). Focusing initially on women,...

Usual Care and Its Variants in the Hierarchy of Control Conditions

The UCs do not necessarily cancel each other out in this type of design because UC may interact differentially with the two conditions. For example, if the remaining ingredients in our example included educational materials about treatments for depression, the participants in the full intervention arm might be more likely than those in the component-only arm to seek non-study antidepressants. This potential source of differential intensification of non-study care should be addressed whenever an RCT is conducted with a UC control group or even when UC is merely present in the trial's milieu. This also holds for EUC, SoC, and IC controls.

Efficacy and Effectiveness Trials

Some efficacy trials in behavioral medicine are analogous to augmentation effectiveness studies, except that the efficacy of the intervention has not yet been established, at least not in the setting of interest or for the population of interest. They compare UC or EUC + an experimental intervention to UC or EUC alone. For example, we recently compared two experimental interventions for depression in patients with a recent history of coronary artery bypass graft (CABG) surgery to UC (Freedland et al, 2009). For simplicity, the present discussion focuses on just one of the interventions, cognitive behavior therapy (CBT). We chose CBT because it had well-established efficacy for depression in psychiatric patients and could be adapted to address the needs and problems of post-CABG patients, but its efficacy had not yet been established in this population. We compared CBT to EUC for depression which, in this patient population, sometimes includes antidepressants but rarely includes...

Factorial Designs in Efficacy Research

Medicine, but they can be very useful. The Canadian Cardiac Randomized Evaluation of Antidepressant and Psychotherapy Efficacy (CREATE) trial (Frasure-Smith et al, 2006 Lesperance et al, 2007) is a good example. Patients with stable coronary disease and major depression were randomly assigned to either clinical management (CM) or interpersonal psychotherapy (IPT) + CM. Within each group, the participants were then randomized to citalopram or to a pill placebo. This yielded four groups IPT + CM + pill placebo, IPT + CM + citalo-pram, CM + pill placebo, and CM + citalopram, and it permitted independent comparisons of citalopram vs. placebo and IPT vs. CM. Because the participants were medical patients, UC was present in the background of all four groups this will be ignored here, for simplicity.

Disorders in Medical Populations

The literature on the relationship between medical illness and psychiatric disorders is mixed. By far the largest literature on comorbid psychiatric problems and medical illness has focused on depressive symptoms and disorders. Chronic medical conditions have generally been associated with increased prevalence of depression and anxiety (Scott et al, 2007). Rates of depression have been shown to be higher among patients with coronary artery disease, particularly following myocardial infarction and stroke (Connerney et al, 2001 Hackett et al, 2005), chronic obstructive pulmonary disease (COPD) 2003). However, even when the prevalence of diagnosable psychiatric disorders is not elevated, this does not mean that there is no distress. For example, among diabetes patients, rates of diagnosable depression have been shown to be similar to the general population, however, sub-threshold depressive symptoms remain elevated (Fisher et al, 2007). anxiety that subside as inflammation decreases...

Natural Depression Cures

Natural Depression Cures

Are You Depressed? Heard the horror stories about anti-depressants and how they can just make things worse? Are you sick of being over medicated, glazed over and too fat from taking too many happy pills? Do you hate the dry mouth, the mania and mood swings and sleep disturbances that can come with taking a prescribed mood elevator?

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