Italian psychiatrists’ perception on cognitive symptoms in major depressive disorder

Objective: Differently than Schizophrenia, the investigation of cognitive impairment in bipolar disorder and major depressive disorder (MDD) attracted the interest of research only recently. Therefore, it is worth understanding clinicians’ perception about cognitive dysfunction in MDD and raising awareness about this issue. Methods: Between December 2014 and January 2015, 128 Italian psychiatrists participated in an on-line survey aiming at understanding psychiatrists’ perception about cognitive symptoms in MDD. The questionnaire comprised three sections: the first investigating psychiatrists’ socio-demographic profile, the second assessing cognitive symptoms relevance without mentioning that they represented the study focus and the third explicitly investigating cognitive symptoms. Results: Cognitive symptoms were considered as a relevant dimension of MDD and appeared among the most frequently cited residual symptoms influencing patients’ work and relapse risk. About 70% of psychiatrists declared that cognitive symptoms significantly influence antidepressant choice. However, in the second questionnaire section cognitive symptoms appeared less frequently considered for antidepressant choice. Conclusions: Results revealed a clear understanding of cognitive symptoms relevance in MDD. Nevertheless, the discrepancy between psychiatrists’ perception and their therapeutical choices underlines the presence of an unmet-need that should be addressed increasing the awareness about the positive effects on cognitive symptoms of existing drugs, which could allow a more symptom-oriented therapeutical intervention.

• Key points

• Major depressive disorder (MDD) is a common mental disorder often associated with deficits in cognitive function.

• Psychiatrists considered cognitive symptoms among the most relevant residual symptoms in MDD patients that compromise patients working and influence the relapse risk.

• The importance given to residual cognitive symptoms seemed not to be reflected by psychiatrists’ therapeutical choice.

• There is a gap between what psychiatrists know and what psychiatrists apply to their clinical practice reflecting the feeling of a therapeutical unmet need.

     

Italian neurologists’ perception on cognitive symptoms in major depressive disorder

The assessment of cognition is an important part of major depressive disorder (MDD) evaluation and a crucial issue is the physicians’ perception of cognitive dysfunction in MDD that remains nowadays a little known matter. The present study aims at investigating the understanding of neurologists’ perception about cognitive dysfunction in MDD. An on-line survey addressed to 85 Italian neurologists in the period between May and June 2015 was performed. The questionnaire comprised three sections: the first section collecting information on neurologists’ socio-demographic profile, the second investigating cognitive symptoms relevance in relation with different aspects and the third one explicitly focusing on cognitive symptoms in MDD. Cognitive symptoms are considered most significant among DSM-5 symptoms to define the presence of a Major Depressive Episode in a MDD, to improve antidepressant therapy adherence, patients’ functionality and concurrent neurological condition, once resolved. Furthermore, an incongruity came to light from this survey: the neurologists considered cognitive symptoms a not relevant aspect to choose the antidepressant treatment in comparison with the other DSM-5 symptoms on one side, but they declared the opposite in the third part of the questionnaire focused on cognitive symptoms. Cognitive symptoms appeared to be a relevant aspect in MDD and neurologists have a clear understanding of this issue. Nevertheless, the discrepancy between neurologists’ perception on cognitive symptoms and the antidepressant treatment highlights the feeling of an unmet need that could be filled increasing the awareness of existing drugs with pro-cognitive effects.     

Cognitive dysfunction in major depression and bipolar disorder: Assessment and treatment options

Cognitive dysfunction is a recognized feature of mood disorders, including major depressive disorder (MDD) and bipolar disorder (BD). Cognitive impairment is associated with poor overall functional outcome and is therefore an important feature of illness to optimize for patients’ occupational and academic outcomes. While generally people with BD appear to have a greater degree of cognitive impairment than those with MDD, direct comparisons of both patient groups within a single study are lacking. There are a number of methods for the assessment of cognitive function, but few are currently used in clinical practice. Current symptoms, past course of illness, clinical features, such as the presence of psychosis and comorbid conditions, may all influence cognitive function in mood disorders. Despite the general lack of assessment of cognitive function in clinical practice, clinicians are increasingly targeting cognitive symptoms as part of comprehensive treatment strategies. Novel pharmacological agents may improve cognitive function, but most studies of standard mood stabilizers, such as lithium and the anticonvulsants, have focused on whether or not the medications impair cognition. Non‐pharmacological strategies, such as cognitive remediation and exercise, are increasingly studied in patients with mood disorders. Despite the growing interest in strategies to manage cognitive function, there is a paucity of high‐quality trials examining either pharmacological or non‐pharmacological modes of intervention.     

Changes in cognitive symptoms after a buspirone–melatonin combination treatment for Major Depressive Disorder

Cognitive deficits are often associated with acute depressive episodes and contribute to the functional impairment seen in patients with Major Depressive Disorder (MDD). Many patients sustain residual cognitive deficits after treatment that may be independent of the core MDD disorder. We tracked changes in cognitive deficits relative to antidepressant treatment response using the patient self-rated Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (MGH-CPFQ) during a 6-week, double-blind trial of a combination antidepressant treatment (buspirone 15 mg with melatonin-SR 3 mg) versus buspirone (15 mg) monotherapy versus placebo in MDD patients with acute depressive episodes. The CPFQ includes distinct cognitive and physical functioning dimension subscales. Treatment response was determined using the Inventory of Depressive Symptomatology (IDSc30). Treatment responders improved significantly more on the total CPFQ than non-responders (p < 0.0001) regardless of treatment assignment. The cognitive dimension of the CPFQ score favored the combination treatment over the other two groups (ANCOVA: p = 0.050). Among the treatment non-responders, the effect size for the CPFQ cognitive dimension was 0.603 favoring the combination treatment over the over two groups and 0.113 for the CPFQ physical dimension. These preliminary findings suggest that a combination of buspirone with melatonin may benefit cognitive function distinct from mood symptoms and that some aspects of cognition may be specific targets for treatment within a population of patients with MDD.     

Duration of untreated illness and depression severity are associated with cognitive impairment in mood disorders

Abstract

Introduction: In this study we estimated the rate and the trajectory of cognitive impairment in a naturalistic sample of outpatients with major depressive disorder (MDD) and bipolar disorder (BD) and its correlation with different variables.

Materials and methods: An overall sample of 109 outpatients with MDD or BD was assessed for multiple clinical variables, including duration of untreated illness (DUI), and tested using the Montreal Cognitive Assessment (MoCA) during Major Depressive Episodes (MDE) and after remission. Correlations between MoCA scores and the clinical variables were then computed.

Results: About 50% of patients with MDD and BD showed mild cognitive impairment during MDE. Improvement of cognitive function between depression and remission was significant, even though residual symptoms were observed especially in the most impaired patients. Of note, cognitive performance during depression was negatively associated with depression severity and DUI.

Discussion: Present findings confirm available evidence about patterns of cognitive impairment in mood disorders, in terms of prevalence and persistence beyond remission in most severe cases. Moreover, a longer DUI was associated with worse cognitive performance during depression, and consequently with poorer outcome, underlining the importance of prompt treatment of these disorders also in light of a cognitive perspective.

• Keypoints

• Although distinct entities, unipolar and bipolar depression determine similar patterns of cognitive impairment in terms of severity and types of altered domains.

• Depression (but not anxiety) severity is associated with cognitive performance in depression.

• Prolonged duration of untreated illness is associated with more severe cognitive impairment during depression, particularly but not specifically in bipolar disorder.

     

Elevated triglyceride levels are associated with cognitive impairments among patients with major depressive disorder

BackgroundCognitive deficits have been identified as one of core clinical symptoms of major depressive disorder (MDD). Accumulating evidence indicated that triglycerides (TG) might be associated with MDD and cognitive decline.ObjectiveThis study examined whether patients with MDD had poorer cognitive functions than healthy controls, and further investigate whether TG levels were involved in MDD, and its cognitive impairments in a Han Chinese population.Method115 patients with MDD and 119 healthy controls were enrolled. Cognitive functions were assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and serum TG levels were examined using enzymatic colorimetry.ResultsTG levels were higher in patients with MDD than healthy controls after controlling for the variables. Cognitive test scores were lower in patients with MDD than healthy controls except for visuospatial/constructional index after controlling for the variables. TG levels were negatively correlated with visuospatial/constructional score, delayed memory score and RBANS total score of MDD. Further multivariate regression analysis showed that TG levels were negatively associated with visuospatial/constructional score, attention score, delayed memory score and RBANS total score of MDD.ConclusionsOur findings supported that serum TG levels might be involved in MDD, and play an important role in cognitive impairments of MDD, especially in delayed memory. Moreover, patients with MDD experienced greater cognitive impairments than healthy controls except for visuospatial/constructional index.     

Factors associated with antidepressant use in depressed and non-depressed community-dwelling elderly: the three-city study

OBJECTIVES: The aim of this study was to identify factors associated with antidepressant use in non-depressed and depressed elderly persons, assuming that they varied according to clinical status. METHODS: We studied 7,868 French community-dwelling subjects aged 65 years and over. The Center for Epidemiological Studies-Depression scale and the Mini International Neuropsychiatric Interview were used to define three groups: non-depressed, high depressive symptoms and current major depressive disorder. Separate analyses were performed to identify the factors which were associated with antidepressant use in each group. RESULTS: Antidepressant use (55% selective serotonin re-uptake inhibitors, 25% tricyclic antidepressants, 20% other types) increased from 4.9% in non-depressed subjects to 17.3% in subjects with high depressive symptoms (HDS) and 33.6% of in those with current major depressive disorder (MDD). The factors associated with antidepressant use varied according to depression status. In particular, men with current MDD were more often treated with antidepressants than women whereas, in both the HDS and the non-depressed groups, antidepressant use was, as has been observed elsewhere, more frequent in women. Gender also had a strong modifying effect on the relationship between antidepressant use and history of major depression. Finally, the direction of the association between antidepressant use and cognitive performance varied according to depression status. CONCLUSIONS: This study showed that the direction and strength of the association between antidepressant use and demographic and health-related factors varied according to the severity of depression symptoms. Further studies are needed to clarify the relationship between gender and cognition and antidepressant use.     

Systematic review of appropriate cognitive assessment instruments used in clinical trials of schizophrenia,major depressive disorder and bipolar disorder

Cognitive dysfunction is increasingly recognized as a symptom in mental conditions including schizophrenia, major depressive disorder (MDD), and bipolar disorder (BPD). Despite the many available cognitive assessment instruments, consensus is lacking on their appropriate use in clinical trials. We conducted a systematic literature review in Embase, PubMed/Medline and PsychINFO to identify appropriate cognitive function instruments for use in clinical trials of schizophrenia, MDD, and BPD. Instruments were identified from the articles. Instruments and articles were excluded if they did not address schizophrenia, MDD, or BPD. Instrument appropriateness was further assessed by the criteria of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative: test–retest reliability, utility, relationship to functional status, potential changeability to pharmacological agents, and tolerability and practicality for clinical trials. The database search yielded 173 articles describing 150 instruments used to assess cognitive function. Seventeen additional instruments were identified through Google and clinicaltrials.gov. Among all these, only 30 (18%) were deemed appropriate for use in the diseases of interest. Of these, 27 were studied in schizophrenia, one in MDD and two in BPD. These findings suggest the need for careful selection of appropriate cognitive assessment instruments, as not all may be valid in these disorders.     

Is a patient‐administered depression rating scale valid for detecting cognitive deficits in patients with major depressive disorder?

Aims: Although cognitive deficits are a common and potentially debilitating feature of major depressive disorder (MDD), such subjective declines in cognitive function are seldom validated by objective methods as a clinical routine. The aim of this study was to validate the Taiwanese Depression Questionnaire (TDQ) for detecting cognitive deficits in a sample of drug‐free patients with MDD. Methods: The subjects consisted of 40 well‐characterized medication‐free patients with MDD and 40 healthy controls. Clinical and neuropsychological assessments, including the Wisconsin Card Sorting Test, the Wechsler Memory Scale–Revised, the Continuous Performance Test, and the Finger‐Tapping Test, were administered at the time of recruitment. Results: Factor analyses of the TDQ yielded three factors. Memory, attention and psychomotor performance were significantly poorer in patients with MDD. The performances of verbal and delayed memory of the Wechsler Memory Scale–Revised were correlated with the cognitive domains of the TDQ. Generalization of our results must be undertaken with caution considering the relatively small sample size, which could lead to increased β‐error. Conclusion: Cognitive subdomains might be considered important for including in patient‐administered questionnaires used to measure symptoms of MDD when developing a new scale.     

Symptom profile of DSM-IV major and minor depressive disorders in first-ever stroke patients.

OBJECTIVE: Depressive disorders are very common in stroke patients. However, vegetative and cognitive symptoms primarily derived from brain damage could hypothetically be indistinguishable from those directly derived from neuropsychiatric disorders, and this could invalidate the diagnostic assessment. Thus, authors aimed to detect the frequency of clinically-rated DSM-IV depressive symptoms and the diagnostic validity of depressive disorders in stroke patients suffering from major depressive disorder (MDD), minor depressive disorder (MIND), and those free of any neuropsychiatric disorders (NODEP). METHODS: First-ever stroke patients (N=200) were approached within 3 months of the acute stroke and were interviewed with the SCID-P and administered the Hamilton Rating Scale for Depression (Ham-D), the Beck Depression Inventory (BDI), the Barthel Index, and the Mini-Mental State Exam. RESULTS: Fifty patients (25%) had MDD, 62 (31%) had MIND, and 88 (44%) had NODEP. Global cognitive level, functional impairment, total scores, and psychic and somatic subscores of the Ham-D and the BDI were different among the three groups. The only symptom that did not differ among patients with MDD, MIND, and NODEP was Feelings of Guilt; all the other eight DSM-IV symptoms were significantly different. In particular, the frequency of Depressed Mood, Diminished Interest or Pleasure, Fatigue or Loss of Energy, Insomnia, and Psychomotor Agitation/Retardation was higher in MIND patients than in NODEP patients. CONCLUSIONS: During the diagnostic procedure for depressive disorders in stroke patients, clinicians should consider equally important vegetative, cognitive, and psychological depressive symptoms, despite their nature.     

Effects of S-adenosylmethionine augmentation of serotonin-reuptake inhibitor antidepressants on cognitive symptoms of major depressive disorder

Major depressive disorder (MDD) is often accompanied by significant cognitive impairment, and there are limited interventions specific to this particular symptom. S-adenosylmethionine (SAMe), a naturally occurring molecule which serves as a major methyl-donor in human cellular metabolism, is required for the synthesis and maintenance of several neurotransmitters that have been implicated in the pathophysiology and treatment of cognitive dysfunction in MDD.ObjectivesThis study is a secondary analysis of a clinical trial involving the use of adjunctive SAMe for MDD.MethodsForty-six serotonin-reuptake inhibitor (SRI) non-responders with MDD enrolled in a 6-week, double-blind, randomized trial of adjunctive oral SAMe were administered the self-rated cognitive and physical symptoms questionnaire (CPFQ), a validated measure of cognitive as well as physical symptoms of MDD, before and after treatment.ResultsThere was a greater improvement in the ability to recall information (P = 0.04) and a trend towards statistical significance for greater improvement in word-finding (P = 0.09) for patients who received adjunctive SAMe than placebo. None of the remaining five items reached statistical significance.ConclusionsThese preliminary data suggest that SAMe can improve memory-related cognitive symptoms in depressed patients, and warrant replication.     

Repetitive Transcranial Magnetic Stimulation Shows Longitudinal Improvements in Memory in Patients With Treatment-Resistant Depression

BackgroundCognitive dysfunction (CD) is a commonly reported symptom of major depressive disorder (MDD). Patients with treatment-resistant depression (TRD) tend to experience greater rates of CD; however, treatment options are limited. Repetitive transcranial magnetic stimulation (rTMS) is effective in treating affective symptoms in patients with TRD, but its potential effect on CD in TRD has not been established.ObjectivesThis study sought to establish the potential cognitive benefits of rTMS in patients with TRD.Materials and MethodsThis study used data from a noninferiority clinical trial investigating two excitatory rTMS protocols to the left dorsolateral prefrontal cortex in unipolar outpatients with TRD. Cognitive testing was performed at baseline and three months posttreatment in 47 patients and a demographically matched cohort of 22 healthy volunteers. Changes in cognitive performance from baseline to posttreatment were assessed using repeated-measures analysis of variance, using both normative and individualized cognitive scoring methods.ResultsPatients with baseline neurocognitive dysfunction showed significant changes in verbal memory at three months posttreatment when using individualized cognitive scoring. Furthermore, improvement in verbal memory within this subset was associated with improvements in affective symptoms.LimitationsThis analysis was performed on a relatively small sample of patients with TRD who were not prescreened for CD and did not include a clinical comparator group.ConclusionsrTMS may be associated with improvements in verbal memory in patients with TRD who present with global CD and who are clinical responders to the treatment. These findings warrant replication in a larger sample as well as further investigations into the neural mechanisms of cognitive improvement after rTMS.     

Acute Efficacy and Safety of Escitalopram Versus Desvenlafaxine and Vortioxetine in the Treatment of Depression With Cognitive Complaint: A Rater-Blinded Randomized Comparative Study

Objective This study aimed to compare the efficacy and safety of escitalopram, vortioxetine, and desvenlafaxine for acute treatment of major depressive disorder (MDD) with cognitive complaint (CC). Methods A total of 129 patients with MDD who also complained of CC were randomized evenly to either escitalopram, vortioxetine, or desvenlafaxine group and underwent a multi-center, six-week, rater-blinded, and head-to-head comparative trial. Differences in depressive symptoms following treatment were measured using the Hamilton Depression Rating Scale (HAMD) and the Montgomery-Åsberg Depression Rating Scale (MADRS). Subjective cognitive function and the presence of adverse events were assessed. Results The three antidepressant treatment groups did not show significant differences in the improvement of depressive symptoms as measured by HAMD and MADRS. Desvenlafaxine treatment was associated with a superior treatment response rate in depressive symptoms compared to vortioxetine or escitalopram treatment. However, no significant differences were found in the remission rate of depressive symptoms. The three antidepressant treatment groups did not show significant differences in the improvement of CC. Adverse profiles of each treatment group were tolerable, with no significant differences. Conclusion In acute antidepressant treatment for MDD with CC, escitalopram, vortioxetine, and desvenlafaxine presented similar efficacy in relief of depressive symptoms; however, desvenlafaxine was associated with a superior treatment. Further studies are needed to confirm these results by investigating the therapeutic efficacy and safety profile of long-term antidepressant treatment of MDD with CC (Clinical Trial Registry, http://cris.nih.go.kr/cris/en/: KCT0002173).     

New hypothesis and treatment targets of depression:an integrated view of key findings

Major depressive disorder(MDD) is a common and devastating psychiatric disorder characterized by persistent low mood,cognitive disorder,and impaired social function. Despite its complex mechanisms,increasing evidence has identified the involvement of neurotrophic factors,inflammatory cytokines,the hypothalamuspituitary-adrenal axis,and glutamate receptors in the pathophysiology of this illness. The present review synthesizes recent research achievements to defi ne the network between different hypotheses of MDD and to understand which part is most pivotal for its pathogenesis. By integrating MDD-related signal pathways,we highlight brain-derived neurotrophic factor(BDNF) dysfunction and increased apoptosis as the fi nal common cascades,and new therapeutic strategies aiming to enhance BDNF function have been shown to exert a rapid and effective antidepressant action.     

The Current Situation on Major Depressive Disorder in China: Research on Mechanisms and Clinical Practice

Depression is the most disabling disorder worldwide that accounts for the highest proportion of global burden attributable to mental disorders. Major depressive disorder(MDD) is characterized by deep sadness, reduced energy,vegetative nervous system dysregulation, cognitive dysfunction, and even a high suicidal tendency. Although other treatment choices are available, antidepressant medication is the front-line treatment option for MDD. Regarding clinical efficacy, only ~50% of patients respond to frontline antidepressants, and <33% obtain remission. Currently, objective indexes to guide clinical decisions are still lacking. Furthermore, knowledge about the neurobiological mechanisms underlying discrepant antidepressant outcomes is still also fragmentary. In the present review, we discuss the current research progress and clinical opinions on MDD in China.     

Longitudinal follow-up of depressive symptoms among normal versus cognitively impaired elderly

OBJECTIVES: This prospectively designed longitudinal study assesses prevalence, incidence and prognosis of depressive symptoms among cognitively normal elderly volunteers compared with patients with mild cognitive impairment (MCI), dementia of Alzheimer type (DAT), and vascular dementia (VAD). Possible relationships between depressive symptoms, cognitive performance, disease types, and effects of antidepressant treatment were analyzed. METHODS: Two hundred and ninety four subjects exhibiting different levels of cognitive performance were admitted to this study. Demographics, cardiovascular and neurodegenerative risk factors, together with measures of neuropsychological test performance, were obtained at sequential visits. Depressive symptoms were selectively treated with antidepressant medications. RESULTS: One hundred and forty six subjects with normal cognition, 19 subjects with MCI, 42 patients with DAT, and 32 patients with VAD were followed for a mean of 3.5 years. With the passage of time, there were trends showing prevalence of depressive symptoms to decrease among DAT and to increase among VAD patients. VAD patients exhibited the highest incidences of new-onset depressive symptoms, followed in incidence by DAT and MCI groups. Depressive symptoms among VAD and MCI patients were more persistent and refractory to antidepressant medications than for DAT patients. Trends suggested that antidepressant treatment might benefit MCI and VAD subjects more than DAT patients. Motivationally related depressive symptoms accounted for major components of elevated Hamilton depression rating scale scores. CONCLUSIONS: Depressive symptoms among DAT patients have higher rates of spontaneous resolution, without requiring intensive drug treatment, than among VAD patients in whom depressive symptoms are more persistent and refractory to drug treatment. Early depressive symptoms among subjects with MCI may represent a preclinical sign and should be considered as a risk factor for impending DAT or VAD among the elderly.     

A meta-analysis of executive dysfunctions in unipolar major depressive disorder without psychotic symptoms and their changes during antidepressant treatment

Wagner S, Doering B, Helmreich I, Lieb K, Tadi? A. A meta‐analysis of executive dysfunctions in unipolar major depressive disorder without psychotic symptoms and their changes during antidepressant treatment. Objective: Empirical evidence supports the existence of significant executive deficits in patients with major depressive disorder (MDD) as compared to non‐depressed controls. Nevertheless, the effect size of executive dysfunctions in unipolar, non‐psychotic MDD as well as their relationship to antidepressant treatment is ambiguous. Method: Meta‐analytic methods were used to assess the severity of executive dysfunctions in unipolar, non‐psychotic MDD as compared to healthy controls and to investigate their course during antidepressant treatment. Results: Fifteen studies comparing the executive functions of 375 patients with DSM‐IV MDD and 481 healthy controls were analysed. Furthermore, in three studies, including 122 patients with MDD, the Stroop test performance was examined before and after antidepressant treatment. Patients with MDD performed 0.439 up to 1.18 (P < 0.0001) standard mean differences worse than healthy controls. The Stroop performance improved during the course of treatment (P = 0.0001). Conclusion: We revealed significant executive dysfunctions in patients with unipolar, non‐psychotic MDD compared with healthy controls and an improvement of the Stroop performance during the course of treatment. Future studies with different test procedures are needed to further investigate the influence of antidepressant treatment on executive functions.     

Drug treatment in depressed elderly in the Dutch community

OBJECTIVES: In older people, a diagnosis of depression is frequently missed, and proper treatment is subsequently hampered. We investigated antidepressant and benzodiazepine use in an older community sample, and assessed possible risk factors associated with non-treatment in depressed elderly. METHODS: Data were used from the baseline measurements of the Longitudinal Aging Study Amsterdam (LASA). In a random, age and sex stratified community sample of 3107 older Dutch people (55 to 85 years), respondents were screened on depression with the Center for Epidemiologic Studies Depression Scale (CES-D). In the depressed subsample depressive disorder according to DSM-III was assessed using the Diagnostic Interview Schedule (DIS). The use of antidepressants and anxiolytics (benzodiazepines) in the depressed subsample was measured, and associations with age, sex, cognitive impairment, physical health and anxiety symptoms were investigated. RESULTS: Only 16% of the respondents with a major depressive disorder used antidepressants. More than half of them used non-therapeutic dosages. Lower antidepressant use was associated with cognitive impairment. Benzodiazepine use was more likely than antidepressant use, which was especially evident in females in the major depressive disorder group. CONCLUSIONS: Depressed older people were undertreated, particularly when they were cognitively impaired. A high rate of benzodiazepine use was found, particularly in females.     

Cognitive therapy does not prevent a response to tryptophan depletion in patients also treated with antidepressants.

BACKGROUND: Acute tryptophan depletion (ATD) induces depressive symptoms in remitted depressed patients treated with serotonergic medications, but not in patients treated with noradrenergic medications or electroconvulsive therapy. A recent study suggests that cognitive therapy (CT) protects against the effects of ATD, but the evidence is questionable. The present study compared the effect of ATD in patients who were treated with antidepressant medication and CT (n = 17) versus antidepressant medication alone (n = 23) during their latest episode. METHODS: Forty remitted depressed patients underwent high-dose and low-dose ATD in a randomized double-blind crossover design. RESULTS: There were no differences in response to ATD between treatment groups. This applied to groups defined by lifetime and by recent CT experience. CONCLUSIONS: Cognitive therapy does not protect against the effects of rapidly lowered plasma tryptophan levels in remitted depressed patients who are also treated with antidepressant medication.     

Cognitive impairment as a risk factor for psychosis

Since the time of Kraepelin and Bleuler, it has been recognized that schizophrenia is associated with a profound and persistent cognitive impairment. This paper reviews the major clinical and epidemiological studies of cognitive functioning in schizophrenia and other psychotic disorders, and presents several possible models to explain the association between cognitive impairment and psychosis. Cognitive impairment is present in the majority of patients with schizophrenia, and, in some, it is already evident in the premorbid stages of the disorder. This cognitive impairment is not secondary to psychotic symptoms, negative symptoms, or socioeconomic status. Cognitive impairment can also be observed in nonpsychotic family members of psychotic patients. On the basis of this evidence, it has been proposed that abnormal cognitive functioning can be considered as a possible causal risk factor for psychosis. Recent studies assessing the relationship between genetic background, cognition, brain function, and schizophrenia are presented here as an outline for future research.