Emotional bias and inhibitory control processes in mania and depression

BACKGROUND: Despite markedly different clinical presentations, few studies have reported differences in neuropsychological functioning between mania and depression. The disinhibited behaviour characteristic of mania and evidence that subgenual prefrontal cortex is differentially activated in mania and depression both suggest that dissociable deficits will emerge on tasks that require inhibitory control and are subserved by ventromedial prefrontal cortex. METHODS: Manic patients and controls undertook computerized neuropsychological tests of memory and planning ability. In addition, manic and depressed patients were directly compared with controls on a novel affective shifting task that requires inhibitory control over different components of cognitive and emotional processing. RESULTS: Manic patients were impaired on tests of memory and planning. Importantly, affective shifting performance of manic patients differed from that of depressed patients. Manic patients were impaired in their ability to inhibit behavioural responses and focus attention, but depressed patients were impaired in their ability to shift the focus of attention. Depressed patients exhibited an affective bias for negative stimuli, and we believe this to be the first demonstration of an affective bias for positive stimuli in manic patients. CONCLUSIONS: Observed impairments on tests of memory and planning suggest a global pathology for mania consistent with previous profiles for this disorder and similar to established profiles for depression. The results on the affective shifting task demonstrate the presence of mood-congruent bias and dissociable components of inhibitory control in mania and depression. Against a background of memory and planning impairments in the two groups, these findings are consistent with a role for the ventromedial prefrontal cortex in mediating mood-cognition relationships.     

Structural brain CT changes and cognitive deficits in elderly depressives with and without reversible dementia ('pseudodementia')

Twenty-six elderly (greater than 60 yrs) patients with DSM-III major depression were compared to 13 patients with NINCDS/ADRDA probable Alzheimer's disease (AD), and to 31 screened normal controls. Subjects were matched on age and sex. Fifteen of the 26 depressed patients were cognitively impaired on the Mini-Mental State Examination (MMSE) upon admission, but after treatment returned to the normal range. These 15 patients were defined as having the dementia syndrome of depression (DOD). The remaining 11 depressed patients were termed depressed, cognitively normal (DCN). All subjects received standardized cranial CT scans for assessment of ventricular brain ratio (VBR) and CT attenuation numbers. Subjects also received neuropsychological evaluation. CT values for the 26 depressed patients lay between those of AD patients and normal controls. CT values for the DOD subgroup clustered near those of AD patients. Patterns of cognitive deficits and correlations of CT attenuation values with cognitive measures were also similar in AD and DOD. Most patients were reassessed at a mean of two years after initial testing; of the 11 of the 15 DOD re-examined, only one had undergone cognitive decline. By contrast, all AD patients retested had declined significantly. Episodes of DOD and DCN tended to 'breed true'. This study suggests that while patients with DOD may have underlying structural brain abnormalities, obvious short-term progression to AD does not commonly occur.     

Abnormal response to negative feedback in depression

BACKGROUND: Recent studies have suggested that subjects with depression suffer a diagnosis-specific motivational deficit, characterized by an abnormal response to negative feedback that endures beyond clinical recovery. Furthermore, it has been suggested that negative feedback may motivate non-depressed controls, but not depressed patients, to improve their performance in neuropsychological tests. METHODS: We describe two studies. The first compared performance on the simultaneous and delayed match to sample (SDMS) task from the CANTAB neuropsychological test battery, in 20 patients with severe depression with 20 with acute schizophrenia, 40 with chronic schizophrenia and 40 healthy controls. The second examined the performance of depressed patients with diurnal variation in symptoms and cognitive function. RESULTS: All patients groups showed impairments on the simultaneous and delayed match to sample task compared to controls. Depressed patients did not show an abnormal response to negative feedback. Controls did not show a motivational effect of negative feedback. Depressed patients with diurnal variation showed no variation in their response to perceived failure. There was no evidence of abnormal response to negative feedback in any patient group using the 'runs test' or of a motivational effect in controls. Conditional probability analysis was not independent of the total number of errors made in the SDMS task. CONCLUSIONS: Further studies are suggested to examine whether an abnormal response to negative feedback characterizes particular subgroups of patients suffering from depression.     

Cognitive function in adults with type 2 diabetes and major depression

The aim of this study was to identify characteristics of neuropsychological functioning among type 2 diabetic adults with and without major depression. Twenty type 2 diabetics with major depression, 20 non-depressed type 2 diabetics and 34 controls without diabetes or depression were compared. A mixed effects repeated measures analysis of covariance indicated significant differences in overall cognitive functioning between diagnostic groups, specifically depressed diabetics demonstrated greater cognitive dysfunction than controls. Further comparisons indicated that depressed diabetics performed significantly worse than non-depressed diabetics in attention/information processing speed. Relative to controls, depressed diabetics performed significantly worse in attention/information processing speed and executive functioning, while there was a trend for non-depressed diabetics to perform worse in executive functioning. These findings suggest that depression negatively impacts cognitive performance among adults with type 2 diabetes, which may have implications for neural circuitry underlying cognitive and mood changes in diabetic patients.     

Deficient inhibition of emotional information in depression

BACKGROUND: There are numerous indications that impaired inhibition of negative affective material could be an important cognitive component of depression. To study whether impaired inhibition of negative affect is a cognitive vulnerability factor explaining (recurrent) depression, inhibition of positive and negative affective stimuli was examined in hospitalized depressed patients, formerly depressed individuals and never-depressed controls. METHODS: To investigate inhibitory dysfunctions in the processing of emotional material, we used an affective modification of the negative priming task with pictures of sad and happy facial expressions. RESULTS: Compared to never-depressed controls, depressed patients showed a specific failure to inhibit negative information, whereas inhibition function for positive material was unaffected. Surprisingly, formerly depressed individuals demonstrated impaired inhibition of negative and positive information. LIMITATIONS: Because of the significant correlations between depression and anxiety self-report scores, the observed reduced inhibitory effect toward negative material in the depression group cannot strictly be attributed as depression-specific. CONCLUSIONS: In accordance with our hypothesis, strongly impaired inhibition of negative affect was found in depressed patients. Based on the present findings, we argue that impaired inhibition of negative affect could be an important construct in cognitive theories on depression linking cognitive biases to neuropsychological impairments in depression. The data in the formerly depressed individuals are less conclusive and several hypotheses are detailed that could explain how the absence of inhibition of affective information could relate to recurrent depression.     

Decision-making cognition in mania and depression

BACKGROUND: Despite markedly different clinical presentations, few studies have reported differences in neuropsychological functioning between mania and depression. Recent work has suggested that differences may emerge on cognitive tasks requiring affective processing, such as decision-making. The present study sought to compare decision-making cognition in mania and depression in order to clarify the current profiles of impairment for these disorders and to contribute to our more general understanding of the relationship between mood and cognition. METHODS: Medicated manic patients, depressed patients, and normal healthy controls completed a computerized decision-making task. All subjects were asked to win as many points as possible by choosing outcomes based on variably-weighted probabilities and by placing 'bets' on each decision. RESULTS: Both patient groups were impaired on this task, as evidenced by slower deliberation times, a failure to accumulate as many points as controls and suboptimal betting strategies. Manic, but not depressed, patients made suboptimal decisions--an impairment that correlated with the severity of their illness. CONCLUSIONS: These findings are consistent with a growing consensus that manic and depressed patients are characterized by significant impairments in cognitive and particularly executive, functioning. Furthermore, the distinct patterns of observed impairment in manic and depressed patients suggests that the nature and extent of cognitive impairment differ between these two groups. Viewed in the context of other recent studies, these findings are consistent with a role for the ventromedial prefrontal cortex in mediating mood-cognition relationships.     

Decreased working memory and processing speed mediate cognitive impairment in geriatric depression

BACKGROUND: While neuropsychological dysfunction is common in geriatric depression, not all aspects of cognition are equally affected. It has been suggested that depressed patients are impaired only in tasks that make heavy demands on processing resources and that a resource decrement therefore underlies the neuropsychological decrements seen in geriatric depression. The present study examined whether processing resources in the form of working memory and information processing speed are decreased in depression and whether a decrease in these resources actually mediates neuropsychological impairment. METHODS: Measures of processing resources were administered to elderly depressed patients prior to treatment and to age-matched controls. Patients whose depression remitted were retested as were the controls. Subjects also received neuropsychological tests of episodic memory and visuospatial performance. RESULTS: Depressed patients performed significantly worse on measures of both processing speed and working memory. While performance on these measures improved in patients whose depression remitted, the amount of improvement was no greater than that seen in the controls with repeat testing. Hierarchical regression analyses showed that depression explained a significant amount of variance on the neuropsychological tasks. However, if the variance associated with processing resources was removed first, depression no longer accounted for a significant amount of neuropsychological variance. CONCLUSIONS: Processing resources are decreased in elderly depressed patients and this decrease in resources appears to mediate impairments in several areas of neuropsychological functioning including episodic memory and visuospatial performance. The resource decrement persists after remission of the depression and thus may be a trait marker of geriatric depression.     

Experimental evidence for a motivational origin of cognitive impairment in major depression

BACKGROUND: Diagnostic criteria and empirical evidence support the existence of cognitive deficits in depression. However, depressed mood, loss of interest and low self-efficacy might influence cognitive performance. METHOD: Goal-setting instructions were used to promote motivation in depressed patients and control subjects during neuropsychological assessment. The resulting performance was compared with performance using standard instructions. Sixty in-patients with non-psychotic unipolar depression and 60 age- and education-matched healthy control subjects were assessed with standard neuropsychological tests [the Auditory Verbal Learning Test (AVLT), the Digit Symbol Test (DST), the Regensburg Word Fluency Test (RWT), and the Number Combination Test (Zahlen-Verbindungs-Test, ZVT)] using either goal-setting or standard test instructions. RESULTS: Depressed patients showed lower baseline performance and lower generalized self-efficacy (p<0.0005) than controls. However, goal-setting instructions significantly improved patients' memory performance by 10% [AVLT: F(5, 54)=3.611, p=0.007] and psychomotor performance by 13% [ZVT: F(3, 56)=3.667, p=0.017]. Consequently, patients and control subjects demonstrated similar results when goal-setting instructions were applied. Goal-setting instructions showed a statistical trend, increasing patients' performance in the DST by 12% [F(1, 58)=2.990, p=0.089], although their verbal fluency measured by the RWT did not increase. No significant correlations of increased performance with generalized self-efficacy were found. CONCLUSIONS: Cognitive deficits in depressed patients are influenced by motivational shortcomings. Because generalized self-efficacy failed to correlate to increased test performance, future research needs to disentangle the effective components of goal-setting instructions. Task-specific self-efficacy as well as enhancement of task-focused attention might underlie the significant goal-setting effect in depressed patients.     

Long-term outcome of depressive pseudodementia in the elderly

BACKGROUND: The term depressive pseudodementia has proved to be a popular clinical concept. Little is known about the long-term outcome of this syndrome. AIMS: To compare depressed elderly patients with reversible cognitive impairment and cognitively intact depressed elderly patients. METHODS: All patients suffering from moderate or severe depression admitted to St Margaret's Hospital, UK as inpatients or day hospital outpatients between January 1 1997 and December 31 1999 (n=182) were screened for entry into the study. Eligible patients were divided into those presenting with pseudodementia and those who were cognitively intact and followed up for 5 to 7 years. RESULTS: Seventy-one point four percent of those suffering from pseudodementia had converted into dementia at follow-up compared to only 18.2% in the cognitively intact group. The relative risk was 3.929 (95% CI: 1.985 to 7.775) and the 'number needed to harm' 1.88. CONCLUSIONS: Reversible cognitive impairment in late-life moderate to severe depression appears to be a strong predictor of dementia. Inpatients and day hospital outpatients with depressive pseudodementia should probably have a full dementia screening, comprehensive cognitive testing and ongoing monitoring of their cognitive function.     

Cognitive functioning in a population-based sample of young adults with a history of non-psychotic unipolar depressive disorders without psychiatric comorbidity

BACKGROUND: There is evidence for cognitive dysfunction in unipolar depression among middle-aged and elderly patients, but cognitive functioning among depressed young adults has scarcely been systematically investigated. The aims of the present study were to examine cognitive functioning among depressed young adults identified from the general population and to determine whether cognitive deficits vary as a function of different disorder characteristics, such as severity and age at onset. METHODS: Performance in verbal and visual short-term memory, verbal long-term memory and learning, attention, processing speed, and executive functioning was compared between a population-based sample of 21-35-year-olds with a lifetime history of non-psychotic unipolar depressive disorders without psychiatric comorbidity (n=68) and healthy controls derived from the same population (n=70). RESULTS: Depressed young adults were not found to be impaired in any of the assessed cognitive functions, except for some suggestion of mildly compromised verbal learning. Nevertheless, younger age at depression onset was associated with more impaired executive functioning. LIMITATIONS: The results may slightly underestimate of the true association between depression and cognitive impairments in the young adult population due to possible dropout of participants. Additionally, the problem of multiple testing was not entirely corrected. CONCLUSION: The findings from this study indicate that a lifetime history of non-psychotic unipolar depressive disorders among young adults without psychiatric comorbidity may be associated only with minimal cognitive deficits, even when some residual depressive symptoms are prevalent. However, early-onset depression may represent a more severe form of the disorder, associated with more cognitive dysfunction.     

Stability and course of neuropsychological deficits in manic and depressed bipolar patients compared to patients with Major Depression

BACKGROUND: Neuropsychological functioning varies across different subgroups of patients with affective disorders; yet there have only been a few studies pointing out distinctive neuropsychological profiles and following-up possible changes in this functioning. The aim of this study was to compare neuropsychological functioning across remitted manic or depressed patients with bipolar disorder compared to remitted patients with Major Depression and to explore the course of their cognitive functioning. METHODS: 30 patients with Major Depression, 17 manic bipolar patients, and 22 depressed bipolar patients were assessed for memory, attention, and executive functions using the Auditory Verbal Learning Test (AVLT), the Modified Card Sorting Test (MCST), the Attention Network Test (ANT), and Stop-Signal Task. Neuropsychological assessment was performed at discharge and seven weeks after discharge. RESULTS: The three groups showed different neuropsychological performance at discharge. Regarding selective attention and speed of responding the manic bipolar patients displayed poorer performance than the other two groups. Furthermore, follow-up assessment revealed that although all patient groups demonstrated an overall improvement, some deficits (especially in executive functions) remain. Manic bipolar patients showed again the worst performance. Depressed bipolar patients, however, were not observed to show a poorer outcome than depressed unipolar patients. CONCLUSIONS: This study provides further evidence for distinct neuropsychological functioning in patients with affective disorders depending on their state of illness. Furthermore, it supports the hypothesis that especially manic bipolar patients stay impaired in certain cognitive functions after remission. These findings may be of clinical relevance regarding treatment and prevention programs and emphasize the need of further research investigating stability and course of patients with mood disorders.     

Dysphoria: self-devaluative and affective components in recovered depressed patients and never depressed controls.

BACKGROUND: The Interacting Cognitive Subsystems analysis of cognitive vulnerability to depression predicts that subjective experiences of dysphoria in recovered depressed patients will be qualitatively different from those of controls. This study tested this prediction using a new instrument, the Depressed States Checklist. METHODS: Twenty-three recovered recurrently depressed patients and 54 never depressed controls rated the affective and self-devaluative components of a dysphoric experience. RESULTS: Groups reported similar levels of affective component but recovered depressed patients reported higher self-devaluative dysphoric experience. At zero affective component of dysphoria neither group reported any self-devaluative feelings. With increasing affective component of dysphoria, the self-devaluative component increased significantly more in recovered patients than in controls. The ratio of self-devaluative to affective components of dysphoria significantly differentiated recovered depressed patients from controls. CONCLUSIONS: As predicted, dysphoria in recovered depressed patients is qualitatively different from controls in ways that increase vulnerability to major depression. The Depressed States Checklist is a new, brief, measure of cognitive vulnerability to depression that may be particularly useful in large, prospective, epidemiological studies.     

Neuropsychological functioning in major depression and responsiveness to selective serotonin reuptake inhibitors antidepressants

BACKGROUND: Only two thirds of patients with major depression (MD) respond to antidepressants. Thus, far applicable predictors of responsiveness to selective serotonergic reuptake inhibitors (SSRIs) have not been found. Cumulative evidence linking serotonergic depletion and cognition led us to hypothesize that the neuropsychological functioning of major depression patients may predict their responsiveness to SSRI antidepressants. METHODS: Fifty-five patients meeting DSM-IV criteria for major depression and strict inclusion and exclusion criteria underwent an extensive clinical and neuropsychological assessment prior to the initiation of selective serotonergic treatment. Following 6 weeks of treatment, severity of depression was reassessed, yielding a responsiveness score by which classification of each subject as a responder or nonresponder was made. The study was double blind. RESULTS: Logistic regression yielded neuropsychological indices, which significantly predicted the probability of depressed patients to respond favorably to SSRIs. Responders were characterized by better functioning in "simple" tasks and by worse functioning in "complex" tasks compared to nonresponders. No differences were found for more lateralized right or left hemisphere functions between responders and nonresponders. LIMITATIONS: Drug treatment comprised of SSRIs but was not standardized. Responsiveness was assessed following 6 weeks of treatment providing for initial amelioration rather than full remission. Placebo response was not controlled for. These limitations may influence the interpretation of the findings. CONCLUSIONS: The present findings suggest that responders and nonresponders to SSRIs might be distinguished by their neuropsychological functioning before treatment. If our findings are replicated, more efficient treatment might be practiced.     

Impaired cognition and decision-making in bipolar depression but no 'affective bias' evident

BACKGROUND: Depression is usually the predominant affective state in bipolar disorder. There are few studies, with discrepant views, examining the extent of cognitive impairment in patients with bipolar depression. To our knowledge, there are no previous studies examining decision-making ability or whether there is an affective attentional bias in bipolar depression. METHOD: We ascertained 24 depressed bipolar I patients from acute psychiatric hospital wards and out-patient clinics and 26 age- and IQ-matched healthy controls. Using computerized tests we evaluated their performance on 'neutral' (non-emotional) cognitive tasks (i.e. memory, attention and executive function) and on novel tasks of emotional cognition (i.e. the decision-making task and the affective go/no-go task). RESULTS: Accuracy measures were significantly impaired on tests of visual and spatial recognition and attentional set-shifting in bipolar depression compared with age- and IQ-matched controls. The quality of decision-making was also significantly impaired in the patients. A mood-congruent attentional bias for 'sad' targets was not evident on the affective go/no-go task. CONCLUSIONS: We found widespread evidence of significant cognitive impairment and impaired quality of decision-making in symptomatically severe depressed bipolar patients. This cognitive impairment may contribute to difficulties with daily living, decision-making and the ability to engage and comply with psychological and drug treatments.     

社区老年期痴呆和老年抑郁症的两年随访研究

目的：了解老年期痴呆和老年抑郁症的疾病过程和转归;动态观察老年人的认知功能变化和情绪改变。方法：以1997年患病率调查时确诊的40例痴呆和25例抑郁症病人以及1528名非病例老人作为随访对象。使用随访问卷进行访谈,诊断流程和标准同1997年。结果：40例痴呆中死亡17例,其标准化死亡比(SMR)为3．42。在23例存活的病人中,8例加重,13例病情不变,1例病情波动,1例诊断为“假性痴呆”;25例老年抑郁症中40％仍为抑郁病例,40％痊愈,20％死亡(其中1例发展为痴呆);非病例老人97年简短心理状况检查(MMSE)低分值组发生痴呆的比率高于97年MMSE分值正常组,97年GDS高分组发生抑郁的比率高于97年整体恶化量表(GDS)分值正常组。结论：老年期痴呆和老年抑郁症的预后差,死亡率高,老年人的认知功能损害与痴呆和抑郁症的发生存在一定的关联,抑郁情绪影响老人的认知功能。     

Cognitive function in depression: a distinct pattern of frontal impairment in melancholia?

BACKGROUND: Although depressed patients demonstrate impaired performance on a range of neuropsychological tests, there is little research that examines either frontal cognitive deficits or possible differences in test performance between melancholic and non-melancholic subtypes. METHODS: Depressed subjects were administered a broad neuropsychological battery. In an overall analysis, 77 depressed subjects were compared with 28 controls. In a second set of analyses, the depressed sample was divided into melancholic and non-melancholic subsets according to DSM-III-R, the CORE system and the Newcastle scale. These depressed subsets were contrasted to controls and with each other using ANCOVA controlling for age, IQ, simple reaction time and Hamilton Depression scores where appropriate. RESULTS: The total depressed sample was impaired on most mnemonic tasks, simple reaction time and Trails B. Similar findings applied to DSM-III-R melancholic and non-melancholic subjects. When defined by the CORE and Newcastle (narrower definitions of melancholia), melancholic patients were additionally impaired on WCST (perseverative response) and (for Newcastle) digit symbol substitution. In contrast, the cognitive performance of the CORE and Newcastle-defined non-melancholic patients was largely unimpaired. CONCLUSIONS: Using narrower definitions of melancholia, i.e. CORE and (in particular) Newcastle, melancholic patients were impaired on mnemonic tasks and tasks of selective attention, and set-shifting while non-melancholic subjects were largely unimpaired in their cognitive performance. These differences may be due to impairment of specific neuroanatomical regions in narrowly defined melancholic patients, in particular the anterior cingulate.     

Stability of negative self-structures: a longitudinal comparison of depressed, remitted, and nonpsychiatric controls

To be considered a vulnerability marker for depression, a variable should, in addition to demonstrating sensitivity and specificity, also show evidence of temporal stability (i.e., remain present in the absence of depressive symptomatology). Although many cognitive factors are associated with depression, the majority of them appear to be episode rather than vulnerability markers. This study examined cognitive organization of positive and negative interpersonal and achievement content in clinically depressed, remitted, and nonpsychiatric controls. At initial assessment, a sample of 54 clinically depressed individuals and 37 never-depressed controls completed self-report measures of positive and negative automatic thoughts and two cognitive organizational tasks. They were retested 6 months later when half of the depressed group no longer met diagnostic criteria for major depression. Negative automatic thoughts decreased and positive automatic thoughts increased significantly in individuals who had improved clinically. The organization of negative interpersonal content remained stable despite symptom amelioration, but negative achievement content was less interconnected at follow-up in those patients who had improved. The structure of relational schemas, in particular, appears to be stable and may be an important cognitive vulnerability factor for depression.     

Distinguishing between neurodegenerative disease and disease-free aging: correlating neuropsychological evaluations and neuropathological studies in centenarians

OBJECTIVE: In an examination of disease-free aging and neurodegenerative disease in 100-year-olds, the New England Centenarian Study compared data from neuropsychological evaluations with postmortem brain studies of fourteen 100-year-olds to ascertain if the presence or absence of Alzheimer disease changes correlated with measured cognitive abilities. METHODS: Fourteen of 74 centenarians who underwent annual extensive neuropsychological evaluation proceeded to postmortem neuropathological examination. CERAD criteria, emphasizing neuritic amyloid plaques and Braak and Braak staging of neurofibrillary tangles were used to assess the 14 brains. RESULTS: Neuropsychological and neuropathological findings correlated well for four subjects with no dementia on testing (CDR = 0) and for six subjects with CDR scores in the dementia range (CDR = 1-5). In the latter group, Alzheimer's disease was diagnosed in four brains; Pick's disease was an etiological factor in the fifth and hippocampal sclerosis in the sixth. Correlation was low for four subjects: two subjects with no dementia on neuropsychological testing met CERAD neuropathological criteria for possible AD; two subjects with dementia on testing did not meet CERAD criteria for definite Alzheimer's disease and had otherwise minimal changes to correlate with the cognitive findings. CONCLUSIONS: Lack of correlation between level of cognitive functioning and brain pathology in two subjects with no dementia raised the question of whether a functional reserve delayed the functional expression of pathological changes. For two subjects with dementia on testing, there appeared to be no sufficient pathological explanation for the extent of the cognitive changes; depression and such factors as environment, sensory impairment, and medical illness may all have played a role. There may also have been neuropathologic changes not detected by current methods.     

Neuropsychological deficits among patients with late-onset minor and major depression.

Cognitive ability of minor depressed patients (N=28), major depressed patients (N=26) and healthy elderly (N=38) was examined cross-sectionally to determine if cognitive abilities of patients with late-onset depression decrease with increasing severity of disease and if cognitive scores for minor depressed patients fall between those of healthy elderly and major depressed patients. A pooled within-group principal component analysis of cognitive test scores identified five components, three of which showed significant group differences. Verbal Recall and Maintenance of Set separated controls from major depressed patients and minor from major depressed patients. Executive Functioning separated controls from minor depressed patients, and Working Memory was borderline for separating controls from major depressed patients. The component representing Nonverbal Recognition was not statistically significant. Partial correlations controlling for age and education indicate that cognitive performance does decrease as severity of depression increases, and the magnitude of the change varies from a trend to a significant deficit depending on the cognitive domain. This decline in cognitive performance parallels a similar trend observed in neuroanatomical studies in which the volume of the frontal and temporal lobes decrease with increasing severity of depression.