Could cognitive vulnerability identify high-risk subjects for schizophrenia?

This review puts into questions the possible role of cognitive vulnerability markers in prediction and prevention of schizophrenia. Until recently, none of the identified cognitive anomalies has been proved to be definitive. However, as new promising candidates are emerging (DS-CPT, CPT-IP, P suppression, Saccadic Eye Movements), the predictive value of these trait-type anomalies may be criticized regarding four issues, which are discussed: technical, metrological, theoretical, and clinical. As things stand, the existence of a cognitive vulnerability marker, which testify to a permanent pathological trait, does not constitute a sufficient factor to identify and treat subjects who are at risk for schizophrenia.     

Is there a role for palmitoylethanolamide in the treatment of depression?

Depression is a common brain disorder affecting about 350 million people worldwide. Although the pharmacological treatment currently available can produce benefits in the majority of cases, residual depressive symptoms, cognitive deficits, functional impairment, and increase in frequency of relapses are frequently present in unipolar and bipolar depressed patients correctly treated. In the last years, numerous evidences have demonstrated the involvement of endocannabinoid system in the pathophysiology of mood disorders. Considering the recent findings about the antidepressant effect of palmitoylethanolamide in animal model, we have hypothesized the potential antidepressant effect of this fatty acid amide in unipolar and bipolar depressed patients.     

Hippuric acid: Could became a barometer for frailty and geriatric syndromes?

Aging is a natural biological event that has some downsides such as increased frailty, decline in cognitive and physical functions leading to chronical diseases, and lower quality of life. There is therefore a pressing need of reliable biomarkers to identify populations at risk of developing age-associated syndromes in order to improve their quality of life, promote healthy ageing and a more appropriate clinical management, when needed. Here we discuss the importance of hippuric acid, an endogenous co-metabolite, as a possible hallmark of human aging and age-related diseases, summarizing the scientific literature over the last years. Hippuric acid, the glycine conjugate of benzoic acid, derives from the catabolism by means of intestinal microflora of dietary polyphenols found in plant-based foods (e.g. fruits, vegetables, tea and coffee). In healthy conditions hippuric acid levels in blood and/or urine rise significantly during aging while its excretion drops in conditions related with aging, including cognitive impairments, rheumatic diseases, sarcopenia and hypomobility. This literature highlights the utility of hippuric acid in urine and plasma as a plausible hallmark of frailty, related to low fruit and vegetable intake and changes in gut microflora.     

Is self-criticism unique for depression? A comparison with social phobia

BACKGROUND: This study further examined the diagnostic specificity of the self-critical personality dimension, as measured by the Depressive Experiences Questionnaire (DEQ; Blatt et al., 1976. The Depressive Experiences Questionnaire. Yale University Press, New Haven). METHODS: Patients with major depression (n=26) were compared to social phobia patients (n=32). RESULTS: Depressed patients scored significantly higher on the DEQ Self-Criticism dimension. However, when current level of depressed mood was controlled for, self-criticism was not a significant predictor of diagnostic status. Further, the level of DEQ self-criticism reported by patients with social phobia was almost three times greater than the level reported in an earlier diagnostic specificity study with panic disorder patients [Bagby et al., 1992. Diagnostic specificity of the dependent and self-critical personality dimensions in major depression. J. Affect. Disord. 26, 59-64]. LIMITATIONS: Only one measure of self-criticism was used in this study, and the research design was cross-sectional rather than prospective. CONCLUSIONS: Self-criticism is not unique to major depression, and this personality dimension may be implicated in other forms of psychopathology [Blatt, 1991. A cognitive morphology of psychopathology. J. Nerv. Ment. Dis. 179, 449-458]. Some cognitive features believed to play an important role in depression may also be salient in persons with social phobia.     

Could treatment of iron deficiency both improve ADHD and reduce cardiovascular risk during treatment with ADHD drugs?

Attention-Deficit/Hyperactivity Disorder (ADHD) is one of the most common childhood-onset neuropsychiatric conditions. Despite extensive research, the etiopathophysiological factors underlying ADHD are not completely understood. It has been suggested that iron deficiency may contribute to ADHD symptoms severity. Whereas evidence from studies based on serum ferritin measures, a marker of peripheral iron status, is somewhat mixed, preliminary recent evidence suggests a deficiency of brain iron in individuals with ADHD. Therefore, it has been proposed that either a deficiency of peripheral iron or a dysfunction of the blood-brain barrier, in the presence of normal peripheral iron levels, may contribute to low brain iron levels, which, in turn, would increase the risk for ADHD symptoms in a subgroup of individuals with this disorder. It has also been found that individuals with ADHD may be at increased risk of severe cardiovascular events during treatment with ADHD drugs, although the extent to which this occurs in ADHD patients compared to non-ADHD individuals is still matter of investigation. Since iron depletion has been recently reported as a risk factor for adverse prognosis in heart failure, iron deficiency might contribute both to ADHD symptoms severity before treatment and to increased risk of severe cardiovascular events during treatment with ADHD drugs in a selected subgroup of patients. Therefore, we hypothesize that the effective treatment of iron deficiency might lead both to improvement of ADHD symptoms severity and to a decrease of the risk of cardiovascular events during treatment with ADHD drugs. If empirical studies confirm this hypothesis, the clinician would be advised to systematically check iron status and effectively treat iron deficiency before starting a pharmacological treatment with ADHD drugs.     

Does illness attribution affect treatment assignment in depression?

Objective: Little is known about depressed individuals' illness attributions and how these influence treatment assignment in clinical practice. The aim of the present study was to examine whether illness attribution across the domains of intraindividual, interpersonal and biological reasons was associated with treatment assignment in a naturalistic treatment setting. Method: Illness attribution was assessed with the Reasons for Depression Questionnaire in 221 depressed individuals. Participants were assigned to either cognitive–behavioural therapy (CBT), interpersonal therapy (IPT) or psychopharmacological treatment (PHT). Results: Depressed individuals who strongly attributed their illness to intraindividual factors were more likely to be assigned to CBT, and depressed individuals attributing their depression to biological reasons were more likely to receive in PHT. In contrast, interpersonal illness attribution was not associated with treatment assignment. Conclusions: Illness attribution influences treatment assignment to CBT and PHT. However, factors other than illness attribution for depression affect a treatment choice of IPT. Copyright © 2009 John Wiley & Sons, Ltd. Key Practitioner Message:

• Intraindividual and biological illness attributions affected depressed individuals' treatment assignment, making these individuals more likely to receive CBT and PHT, respectively.
• Interpersonal illness attribution was not found to be associated with treatment assignment.
• There were significant gender differences in illness attribution. Men were more likely to endorse in achievement‐related causes, and women attributed their depressive illnesses to more interpersonal reasons (i.e., relationship, childhood and intimacy).

     

Could decitabine treatment impair memory functions in humans?

The role of epigenetic mechanisms in cognitive functions and neurological/psychiatric disorders has been studied in a number of studies recently. One of these mechanisms is DNA methylation, for which DNA methyltransferases (DNMT) are responsible. Decitabine, or 5-aza-2′-deoxycytidine, is a cytosine-analog DNMT inhibitor and is used in the treatment of certain myelodysplastic syndromes (MDS) subsets. Several studies address the role of DNA methylation and negative effects of decitabine on memory formation and consolidation in animals. We, therefore, hypothesize that standard decitabine treatment for MDS in patients without dementia might cause learning and memory deficits. A clinical trial is proposed to test the hypothesis which could support the role of DNA methylation in cognitive abilities of humans.     

Is gender a factor in psychiatrists' evaluation and treatment of patients with major depression?

BACKGROUND: Gender differences in clinical assessment and treatment have been reported in several areas of medicine. We examine whether differences exist in the routine outpatient psychiatric management of men and women with major depression. METHODS: Psychiatrists practicing in the community completed case forms on a systematic sample of their adult outpatients with major depression. Comparisons are presented between male (n=261) and female (n=472) patients focusing on their background characteristics, clinical presentation, assessment, and treatment. Significant gender disparities in assessment and treatment are also examined with respect to the gender of the treating psychiatrist. RESULTS: Although male and female patients had generally similar clinical profiles, a significantly greater proportion of males than females had psychomotor retardation and substance use disorders. No significant gender differences were observed in the assessment of depressive symptoms, psychiatric comorbidities, and treatment with antidepressant medications or psychotherapy. However, a significantly smaller percentage of depressed women than men received assessments of sexual function and medication-related sexual side effects. Female patients were also less likely to have discussed their treatment preferences with their psychiatrists. LIMITATIONS: Only a minority (33.2%) of psychiatrists invited to participate contributed patients to this study. The results are based on structured assessments completed by practicing psychiatrists rather than patient self-assessments or independent research assessments. CONCLUSIONS: Although we find overall little evidence of gender bias in the clinical management of major depression, both male and female psychiatrists need to further explore sexual function and treatment preferences in female patients.     

The treatment of psychotic major depression: is there a role for adjunctive psychotherapy?

BACKGROUND: Psychotic depression is a relatively prevalent mood disorder associated with greater symptom severity, a poorer course of illness and higher levels of functional impairment compared with nonpsychotic depression. Separate lines of investigation suggest that various forms of cognitive-behavioral therapy are efficacious for treating severe forms of nonpsychotic depression as well as primary psychotic disorders. However, there currently are no empirically supported psychotherapies specifically designed for treating psychotic depression. METHOD: We review the efficacy of current somatic treatments for the disorder and discuss the limited data to date on potentially useful psychotherapeutic approaches. In particular, we describe the clinical improvement observed in a subgroup of hospitalized patients with psychotic depression treated with Acceptance and Commitment Therapy as part of a larger clinical trial. RESULTS: Pilot results demonstrated that Acceptance and Commitment Therapy was associated with clinically significant reductions in acute symptom severity and impairment compared with treatment as usual. CONCLUSION: The findings suggest that patients with psychotic depression can benefit from psychotherapy. Clinical and research recommendations in this area are presented.     

Is methoxydine a new rapid acting antidepressant for the treatment of depression in alcoholics?

Methoxydine is a dissociative anaesthetic belonging to the arylcyclohexylamine class. This substance shows pharmacodynamic similarities with ketamine, a medication with demonstrated rapid-acting antidepressant effects. Like ketamine, results of binding assays have shown that methoxydine is an uncompetitive antagonist of NMDA receptor approximately as potent as ketamine, but less potent than PCP. Furthermore, unlike ketamine, it acts as a dopamine, serotonin, and noradrenaline reuptake inhibitor as well as an agonist at sigma-1, sigma-2, and opioid receptors. The hypothesis is that methoxydine can produce rapid antidepressant effects in depressed patients with high risk of suicide, including depressed alcoholics.     

Could 13C MRI assist clinical decision-making for patients with heart disease?

Even at this early stage of development, it is clear that the imaging of hyperpolarized (13)C-enriched molecules and their metabolic products offers a new approach to the study of the physiology and disease of the heart. The technology is practical in humans and, for this reason, we consider whether a role in clinical decision-making should motivate further development. The range of interventions available to treat coronary and valvular heart disease is already extensive, and new options are imminent. Yet the appropriate management of patients with left ventricular dysfunction can be challenging because the mechanism of reduced function may be unclear and the ability of the ventricle to respond to therapy may be difficult to predict. Pyruvate is a promising early target for development as a diagnostic agent because it lies at a critical branch point in cardiac biochemistry. The rate of metabolism of hyperpolarized pyruvate to CO(2) relative to lactate may prove to be a useful indicator of preserved mitochondrial function, and therefore provide a specific signal of viable myocardium. Other species including physiological substrates and nonphysiological molecules may provide additional information. Once suitable technology becomes available, it is likely that clinical research will progress quickly. The ability to monitor directly specific metabolic pathways may lead to an improvement in the selection of patients who will benefit from interventions, pharmacologic or otherwise.     

Is extended clonazepam cotherapy of fluoxetine effective for outpatients with major depression?

Background: Clonazepam cotherapy of fluoxetine was previously demonstrated to accelerate efficacy over the first 3 weeks of treatment. A new 18-week double-blind study attempted to replicate these findings to determine whether superiority would extend to 3 months and assess risks of extension. Method: Fifty outpatient volunteers aged 18–65 from Seattle and Portland with moderate-marked depression received fluoxetine (20 mg) doubled at 6 weeks if needed; half took clonazepam (0.5 mg) and half took an identical placebo, 1 or 2 tablets adjusted during the first 2 weeks, until a 3-week taper at 3 months. Results: No serious adverse events and no special problems with sedation or discontinuation were noted. Cotherapy was superior to fluoxetine monotherapy at Day 7 for HAM-D (t=2.03, DF=48, P<0.05) and CGI-I (32 vs. 4% responders, P<0.03, Fisher Exact Test) but not otherwise. Cotherapy was effective in reducing insomnia but not anxiety or core symptoms (low mood, suicidality, reduced interest). The only significant benefit of extending treatment was a more rapid response to increased fluoxetine at 6 weeks manifested in a mean HAM-D of 9.0 and CGI-I responder rate of 76% after 8 weeks compared to 16 weeks for monotherapy. Limitations: Small sample size (N=50) limited power and rendered conclusions tentative. Conclusions: Extended clonazepam cotherapy of fluoxetine appeared safe and effective for depressed outpatients: it was superior to fluoxetine alone early in treatment and again following fluoxetine dose increase. Cotherapy might be considered at the start of fluoxetine treatment, especially for those with insomnia, and when a dose increase of fluoxetine is anticipated.     

Could positive diurnal variations in severe depression be the key factor for delivering effective cognitive behaviour therapy?

Cognitive behaviour therapy (CBT) has been demonstrated to be the leader in the field of talking therapies concerned with the treatment of severe depression.However, this form of therapy has its limitations in that it is ineffective if given during a severe depressive episode. This is usually because patients suffering from severe depression have difficulties in concentration which severely limits the ability to take in new information such as the practice of strategies that encourage more helpful ways of thinking which could aid recovery.The severely depressed patient who experiences diurnal variations typically experiences low mood in the morning but mood improves towards the evening. Conversely, there are cases where mood is better in the morning becoming worse in the evening. There can be cases of positive diurnal rhythms where adverse symptoms disappear all together and the patient regains something resembling their pre-morbid normality.With this lifting of mood, it could mean that the patient may be more receptive to absorbing new information. Consequently, the hypothesis is that when patients are experiencing positive diurnal rhythms, this could be the optimum time to deliver effective talking treatments such as CBT.     

Is there evidence for a male depressive syndrome in inpatients with major depression?

BACKGROUND: The question is investigated whether atypical depressive symptoms such as irritability, anger attacks, aggressiveness or abusive behavior, which are hypothesized to indicate a hypothetical male depressive syndrome are more prevalent in male than in female inpatients with unipolar major depression. METHODS: Data were obtained from 2411 patients who had been consecutively admitted to the Department of Psychiatry of the Ludwig-Maximilians-University of Munich. Psychopathological symptoms had been assessed by a standardized documentation system (AMDP). RESULTS: Neither frequency nor mean scores of most of the symptoms describing a male depressive syndrome differed between males and females. There were no gender differences in symptoms with respect to severity of depression, first hospitalization and duration of illness. However, gender differences emerged when regarding symptom patterns by factor analysis. Limitations: Only inpatients were studied, and comorbidity was not considered. CONCLUSIONS: The hypothesis of a male depressive syndrome needs further research, focusing on the gradual development of (masked) depression by men in mainly non-clinical samples.