Do antidepressants change personality?--a five-year observational study.

BACKGROUND: Whether antidepressants influence personality is a major clinical and societal issue due to their widespread use. In an observational study, we investigated whether depressive patients' neuroticism and extraversion scores covary with antidepressant pharmacotherapy, and if so, whether this remains significant after accounting for depressive or anxiety symptoms. METHODS: Major depressive disorder patients (N=237) were interviewed at up to four time-points in a five-year prospective longitudinal study. Changes in neuroticism plus extraversion scores were compared with changes in antidepressant pharmacotherapies and depressive plus anxiety symptoms to uncover any covariation between them. Autoregressive path models were used to examine this covariation at the sample level. Within-subject change was estimated using a random-effects latent change model. RESULTS: Significant covariation is present in the change trajectories between personality scores and depressive symptoms; declining depression scores were associated with rising extraversion and declining neuroticism. Although the personality scores of many patients changed significantly over the five-year study, none of these changes were associated with changes in antidepressant pharmacotherapy. LIMITATIONS: The study covered only two dimensions of personality. Single drug-specific analysis could not be done. Antidepressant blood levels were not measured. CONCLUSION: No evidence emerged for significant covariation of antidepressant pharmacotherapy with neuroticism or extraversion scores. By contrast, changes in both personality dimensions were associated with changes in depressive symptoms, those in neuroticism also in anxiety symptoms. If antidepressants influence these personality dimensions, the effect size is likely markedly smaller than that of the disorders for which they are prescribed.

P2RX7 gene is associated consistently with mood disorders and predicts clinical outcome in three clinical cohorts.

We investigated the effect of nine candidate genes on risk for mood disorders, hypothesizing that predisposing gene variants not only elevate the risk for mood disorders but also result in clinically significant differences in the clinical course of mood disorders. We genotyped 178 DSM-IV bipolar I and II and 272 major depressive disorder patients from three independent clinical cohorts carefully diagnosed with semistructured interviews and prospectively followed up with life charts for a median of 60 (range 6-83) months. Healthy control subjects (n = 1322) were obtained from the population-based national Health 2000 Study. We analyzed 62 genotyped variants within the selected genes (BDNF, NTRK2, SLC6A4, TPH2, P2RX7, DAOA, COMT, DISC1, and MAOA) against the presence of mood disorder, and in post-hoc analyses, specifically against bipolar disorder or major depressive disorder. Estimates for time ill were based on life charts. The P2RX7 gene variants rs208294 and rs2230912 significantly elevated the risk for a familial mood disorder (OR = 1.35, P = 0.0013, permuted P = 0.06, and OR = 1.44, P = 0.0031, permuted P = 0.17, respectively). The results were consistent in all three cohorts. The same risk alleles predicted more time ill in all cohorts (OR 1.3, 95% CI 1.1-1.6, P = 0.0069 and OR 1.7, 95% CI 1.3-2.3, P = 0.0002 with rs208294 and rs2230912, respectively), so that homozygous carriers spent 12 and 24% more time ill. P2RX7 and its risk alleles predisposed to mood disorders consistently in three independent clinical cohorts. The same risk alleles resulted in clinically significant differences in outcome of patients with major depressive and bipolar disorder.

Differences in neuroticism and extraversion between patients with bipolar I or II and general population subjects or major depressive disorder patients.

BACKGROUND: Whether levels of neuroticism or extraversion differ between patients with bipolar disorder (BD), major depressive disorder (MDD) and subjects from the general population, or between BD I and BD II patients, remains unclear. METHODS: BD patients (n=191) from the Jorvi Bipolar Study, and MDD patients (n=358) from both the Vantaa Depression Study and the Vantaa Primary Care Depression Study cohorts, were interviewed at baseline and at 18 months. A general population comparison group (n=347) was surveyed by mail. BD patients' neuroticism and extraversion scores, measured by Eysenck Personality Inventory, were compared at an index interview, when the levels of depression and mania were lowest, with scores of MDD patients and general population controls. Comparisons were also made between BD I (n=99) and BD II (n=92) patients. RESULTS: In multinomial logistic regression, BD patients had higher neuroticism (OR=1.17, p<0.001) and lower extraversion (OR=0.92, p=0.003) than the general population. When entered simultaneously into the model, the effect of extraversion disappeared. In logistic regression, the levels of neuroticism and extraversion did not differ between BD and MDD patients, or between BD I and II patients. LIMITATIONS: Patients' personality scores were not pre-morbid. CONCLUSIONS: Levels of neuroticism and extraversion are unlikely to differ between BD and MDD patients, or between BD I and II patients. The overall level of neuroticism is moderately higher and extraversion somewhat lower in BD patients than in the general population. High neuroticism may be an indicator of vulnerability to both bipolar and unipolar mood disorders.

Categorical and dimensional stability of comorbid personality disorder symptoms in DSM-IV major depressive disorder: a prospective study.

OBJECTIVE: To investigate the categorical and dimensional temporal stability of Axis II personality disorders among depressive patients, and to determine whether variations in Axis I comorbid disorders or self-reported personality traits predict changes in researcher-assigned personality disorder symptoms. METHOD: Patients with DSM-IV major depressive disorder (MDD) in the Vantaa Depression Study (N = 269) were interviewed with the World Health Organization Schedules for Clinical Assessment in Neuropsychiatry, version 2.0, and the Structured Clinical Interview for DSM-III-R Axis II Disorders and were assessed with the 57-item Eysenck Personality Inventory at baseline, 6 months, and 18 months. Baseline interviews occurred between February 1, 1997, and May 31, 1998; follow-up interviews were 6 months and 18 months after baseline for each patient. Of the patients included in the study, 193 remained unipolar and could be interviewed at both follow-ups. The covariation of the severity of depression, anxiety, alcohol use, and reported neuroticism and extraversion with assigned personality disorder symptoms was investigated by using general estimation equations. RESULTS: The diagnosis of personality disorder persisted at all time points in about half (43%) of the 81 MDD patients diagnosed with personality disorder at baseline. The number of positive personality disorder criteria declined, particularly during the first 6 months, by a mean of 3 criteria. The decline in reported personality disorder symptoms covaried significantly with declines in the severity of depressive and anxiety symptoms (depressive: P = .02 for paranoid, P = .02 for borderline, and P = .01 for avoidant; anxiety: P = .08 for paranoid, P = .01 for borderline, and P < .001 for avoidant). Changes in patients' perceptions of self as measured by neuroticism covaried with changes in paranoid (P = .01) and borderline (P < .001) personality disorder symptoms. CONCLUSIONS: Among MDD patients, the categorical stability of concurrent personality disorder diagnoses assigned while depressed is relatively poor, but the dimensional stability is moderate. The remission of depression as well as variations in Axis I comorbidity, particularly anxiety disorders, influences personality disorder diagnoses. These diagnostic difficulties most likely reflect broader variations in patients' perceptions of self over time, not merely psychometric problems related to the pertinent diagnostic criteria.

Major depressive disorder and white matter abnormalities: a diffusion tensor imaging study with tract-based spatial statistics.

BACKGROUND: A few diffusion tensor imaging (DTI) studies have shown abnormalities in areas of white matter tracts involved in mood regulation in geriatric depressive patients, using a region-of-interest technique. A voxel-based morphometry DTI study of young depressive patients reported similar results. In this study, we explored the structure of the white matter of the whole brain with DTI in middle-aged major depressive disorder (MDD) patients, using novel tract-based spatial statistics. METHODS: Sixteen MDD patients and 20 controls underwent DTI. An automated tract-based spatial method (TBSS) was used to analyze the scans. RESULTS: Compared with controls, the MDD patients showed a trend for lower values of fractional anisotropy (FA) in the left sagittal stratum, and suggestive decreased FA in the right cingulate cortex and posterior body of corpus callosum. Regressing out the duration and severity of disorder in the model did not change the finding in the sagittal stratum, but dissipated the decrease of FA in latter regions. LIMITATIONS: Possibly by reason of a relatively small study sample for a TBSS, the results are suggestive, and should be replicated in further studies. CONCLUSIONS: A novel observer-independent DTI method showed decreased FA in the middle-aged MDD patients in white matter regions that have previously connected to the emotional regulation. Lower FA might imply underlying structural abnormalities that contribute to the dysfunction detected in the limbic-cortical network of depressive patients.

Influence of personality on objective and subjective social support among patients with major depressive disorder: a prospective study.

Personality and social support (SS) influence risk for depression and modify its outcome through multiple pathways. The impact of personality dimensions neuroticism and extraversion on SS among patients with major depressive disorder (MDD) has been little studied. In the Vantaa Depression Study, we assessed neuroticism and extraversion with the Eysenck Personality Inventory, objective SS with the Interview Measure of Social Relationships, and subjective SS with the Perceived Social Support Scale-Revised at baseline, at 6 and 18 months among 193 major depressive disorder patients diagnosed according to the fourth edition of Diagnostic and Statistical Manual of Mental Disorders (DMS-IV). At all time-points, low neuroticism and high extraversion associated significantly with between-subject differences in levels of objective and subjective SS. Lower neuroticism (beta = 0.213, p = 0.003) and higher extraversion (beta = 0.159, p = 0.038) predicted greater within-subject change of subjective, but not objective SS. Thus, neuroticism and extraversion associated with the size of objective and subjective SS and predicted change of subjective SS. Modification of subjective SS, particularly, may indirectly influence future vulnerability to depression.

Neuroticism, introversion, and major depressive disorder--traits, states, or scars?

BACKGROUND: The extent to which measures of the personality dimensions of neuroticism and introversion are influenced by symptoms of depression and anxiety or by episodes of depression, and whether neuroticism alone or both traits predispose one to depression remain unclear. METHODS: Major depressive disorder patients (n=193) from the Vantaa Depression Study were interviewed at baseline and at 6 and 18 months, and a general population comparison group (n=388) was surveyed by mail. Patients' scores of neuroticism and extraversion-introversion were compared between time points, and before and after a possible recurrence of depression between interviews. Patients' scores at an index interview, when the level of depression was lowest, were compared with scores of the general population, after controlling for anxiety and depression. RESULTS: Among depressive patients, neuroticism scores declined (from 17.2, SD 3.7-13.7, SD 5.6, P<0.001) and extraversion scores increased (from 10.0, SD 4.7-11.2, SD 4.5, P<0.001) with recovery during follow-up. The scores were not influenced by a recurrence of depression between measurements. In logistic regression, patients had higher neuroticism (odds ratio, OR 1.11, P=0.001) and lower extraversion (OR 0.92, P=0.003) than the general population. CONCLUSIONS: The overall level of neuroticism is markedly and introversion somewhat higher in depressive patients than in the general population. Anxiety symptoms have some, and depressive symptoms a strong influence on neuroticism scores, but only depression has an impact on introversion during a depressive episode. In medium-term follow-up, depressive episodes are unlikely to result in a personality scar persisting after recovery from an episode.

The influence of major depressive disorder on objective and subjective social support: a prospective study.

The impact of persistent depression on social support (SS) is not well known. In the Vantaa Depression Study (VDS), 193 patients with DSM-IV MDD were interviewed at baseline, at 6 and 18 months. Objective SS was measured with the Interview Measure of Social Relationships (IMSR), and subjective SS with the Perceived Social Support Scale-Revised (PSSS-R); the influence of time spent in major depressive episodes (MDEs) on SS at 18 months was investigated. Low objective SS was independently predicted by low baseline objective SS, male gender, and longer time spent in MDEs; low subjective SS by longer time spent in MDEs and lower baseline subjective SS. Along with clinical improvement, subjective SS improved but objective SS did not. The persistence of MDD seems to weaken both objective and subjective SS. Whether this results in progressively weakening objective and subjective SS, and thereby lowers the threshold for future depressive episodes, should be further investigated.

Adequacy of, attitudes toward, and adherence to treatments by suicidal and nonsuicidal depressed patients.

We examined differences in treatments received, and attitudes and adherence to them between suicidal and nonsuicidal patients with major depressive disorder (MDD). Psychiatric MDD patients with no suicidal behavior (N = 92), suicidal ideation (N = 92), or attempts (N = 34) were compared during 6 months of follow-up in the Vantaa Depression Study (VDS). Patients with suicidal behavior received antidepressants or adequate antidepressant treatment significantly more often, had more frequent appointments with psychiatrists, more psychotherapeutic support, and more favorable attitudes toward antidepressant treatment than nonsuicidal patients. However, after adjusting for the confounding severity of depression, the significance of these differences was lost. Adherence to treatment was similar in the patient groups. Overall, among psychiatric patients with MDD, those known to be suicidal have higher suicide risk and should receive more intensive treatment. However, suicidal behavior per se does not seem to markedly influence treatments provided nor should it be associated with negative attitudes or poor adherence to treatments.

Long-term outcome of major depressive disorder in psychiatric patients is variable.

OBJECTIVE: The prevailing view of outcome of major depressive disorder (MDD), based on mostly inpatient cohorts sampled from tertiary centers, emphasizes chronicity and frequent recurrences. We investigated the long-term outcome of a regionally representative psychiatric MDD cohort comprising mainly outpatients. METHOD: The Vantaa Depression Study included 163 patients with DSM-IV MDD (71.5% of those eligible) diagnosed using structured and semistructured interviews and followed up at 6 months, 18 months, and 5 years with a life chart between February 1, 1997, and April 30, 2004. The effects of comorbid disorders and other predictors on outcome were comprehensively investigated. RESULTS: Over the 5-year follow-up, 98.8% of patients achieved a symptom state below major depressive episode (MDE) criteria, and 88.4% reached full remission, with the median time to full remission being 11.0 months. Nearly one third (29.3%) had no recurrences, whereas 30.0% experienced 1, 12.9% experienced 2, and 27.9% experienced 3 or more recurrences. Preceding dysthymic disorder (p = .028), cluster C personality disorder (p = .041), and longer MDE duration prior to entry (p = .011) were the most significant predictors of longer time in achieving full remission. Severity of MDD and comorbidity, especially social phobia, predicted probability of, shorter time to, and number of recurrences. CONCLUSION: Previous literature on mostly inpatient MDD may have, by generalizing from patients with the most severe psychopathology, overemphasized chronicity of MDD. The long-term outcome of MDD in psychiatric care is variable, with about one tenth of patients having poor, one third having intermediate, and one half having favorable outcomes. In addition to known predictors, cluster C personality disorders and social phobia warrant further attention as predictors of MDD outcome among outpatients.

Dysfunction in early auditory processing in major depressive disorder revealed by combined MEG and EEG.

BACKGROUND: Patients with major depressive disorder (MDD) show impairments in cognitive functions. However, neural mechanisms underlying these disturbances are poorly understood. We investigated whether MDD affects neural mechanisms of involuntary attention studied by auditory evoked potentials (AEPs) and auditory evoked magnetic fields (AEFs). METHODS: AEPs and AEFs were studied in a passive odd-ball paradigm in 13 drug-free patients with unipolar MDD during an acute episode and 12 age-and sex-matched healthy subjects. Auditory responses to monaurally presented frequent "standard" tones, infrequent "deviant" tones (10% and 20% frequency change) and occasional "novel" sounds (complex sounds) were simultaneously recorded with whole-head magnetoencephalography (MEG) and electroencephalography (EEG). RESULTS: P1 and P1m latencies were decreased in patients with MDD, compared with those in healthy subjects. Further, the mismatch negativity amplitude to the 10% frequency deviance in the EEG, but not in the MEG, was increased in MDD. We observed no differences in N1/N1m and P3a responses in the MEG and EEG. The magnitude of decrease in P1/P1m latency correlated negatively with the severity of depression in the patients. CONCLUSIONS: Early auditory processing is impaired in patients with MDD during an acute episode, probably reflecting dysfunctional frontotemporal neural circuits. These dysfunctions may contribute to the cognitive disturbances observed in people with MDD.

Do characteristics of patients with major depressive disorder differ between primary and psychiatric care?

BACKGROUND: Despite the need for rational allocation of resources and cooperation between different treatment settings, clinical differences in patients with major depressive disorder (MDD) between primary and psychiatric care remain obscure. We investigated these differences in representative patient populations from primary care versus secondary level psychiatric care in the city of Vantaa, Finland. METHOD: We compared MDD patients from primary care in the Vantaa Primary Care Depression Study (PC-VDS) (n=79) with psychiatric out-patients (n=223) and in-patients (n=46) in the Vantaa Depression Study (VDS). DSM-IV diagnoses were assigned by the Structured Clinical Interview for DSM-IV Axis I disorders (SCID-I in PC-VDS) or Schedules for Clinical Assessment in Neuropsychiatry (SCAN in VDS), and SCID-II interviews. Comparable information was collected on depression severity, Axis I and II co-morbidity, suicidal behaviour, preceding clinical course, and attitudes towards and pathways to treatment. RESULTS: Prevalence of psychotic subtype and severity of depression were highest among in-patients, but otherwise few clinical differences between psychiatric and primary care patients were detected. Suicide attempts, alcohol dependence, and cluster A personality disorder were associated with treatment in psychiatric care, whereas cluster B personality disorder was associated with primary care treatment. Patients' choice of the initial point of contact for current depressive symptoms seemed to be independent of prior clinical history or attitude towards treatment. CONCLUSIONS: Severe, suicidal and psychotic depression cluster in psychiatric in-patient settings, as expected. However, MDD patients in primary care or psychiatric out-patient settings may not differ markedly in their clinical characteristics. This apparent blurring of boundaries between treatment settings calls for enhanced cooperation between settings, and clearer and more structured division of labour.

Impaired functional connectivity at EEG alpha and theta frequency bands in major depression.

Recent reports on functional brain imaging in major depression have lead to an assumption that observed psychopathology might be related to an altered brain functional connectivity. Our hypothesis was that an increase in brain functional connectivity occurs in major depression. As a measure of functional connectivity, the electroencephalogram (EEG) structural synchrony approach was used in 12 medication-free depressive outpatients and 10 control subjects. Differences in the number and strength of structurally synchronized EEG patterns were compared between groups. In depressive patients the number and strength of short cortex functional connections were significantly larger for the left than for the right hemisphere, while the number and strength of long functional connections were significantly larger for the right than for the left hemisphere. Some of the functional connections were positively correlated with the severity of depression, thus being predictive. These were short-range anterior, posterior, and left hemisphere functional connections for the alpha frequency band and short-range anterior functional connections for the theta frequency band. The topology of the most representative functional connections among all patients with major depression indicated that the right anterior and left posterior brain parts may discriminate depressive patients from healthy controls. The obtained data support our hypothesis that there is an increase in brain functional connectivity in major depression. This finding was interpreted within the semantic framework, where different specialization of left (monosemantic context) and right (polysemantic context) hemispheres is functionally insufficient in patients with depression.

Determinants of functional disability and social adjustment in major depressive disorder: a prospective study.

We examined prospectively factors influencing social and occupational disability and social adjustment among patients with major depressive disorder. The Vantaa Depression Study comprises a cohort of psychiatric inpatients and outpatients with major depressive disorder in the city of Vantaa, Finland. We prospectively interviewed 193 of 269 (72%) patients both 6 and 18 months after baseline. Axis I and II diagnoses were assessed via semistructured WHO Schedules for Clinical Assessment in Neuropsychiatry 2.0 and SCID-II interviews. Global disability and social and work adjustment were assessed. Patients' functional disability and social adjustment were alleviated concurrently with recovery from depression during the follow-up. The current level of functioning and social adjustment of a patient with depression was predicted by severity of depression, recurrence before baseline and during follow-up, lack of full remission, and time spent depressed. Comorbid psychiatric disorders, personality traits (neuroticism), and perceived social support had significant influence.

Composition of brain oscillations in ongoing EEG during major depression disorder.

In the present study, we examined the composition of electroencephalographic (EEG) brain oscillations in 12 unmedicated major depressive outpatients and 10 healthy subjects during resting conditions (closed eyes). The exact composition of brain oscillations was assessed by the probability-classification analysis of short-term EEG spectral patterns. In contrast to previous studies of depression, the current study found that major depression affects brain activity in nearly the whole cortex and manifests itself in considerable reorganization of the composition of brain oscillations in a broad frequency range: 0.5-30 Hz. At the same time, the magnitude of the effect of depression was maximal in the posterior cortex of the brain. Interhemisphere asymmetry during major depression was also observed in the whole cortex with right hyperactivity in frontal, parietal and occipital brain areas. It is suggested that depressive brain is manifested in the superposition of distributed multiple oscillations. Our findings provide new insight on the relationship between major depressive disorder and cortical oscillatory activity.

Decline in suicidal ideation among patients with MDD is preceded by decline in depression and hopelessness.

BACKGROUND: Suicidal ideation is likely to represent a phase preceding suicidal acts among most suicidal patients with major depressive disorder (MDD). Factors predicting reversal of the suicidal process are unknown. Our aim was to test the hypothesis that a decline in suicidal ideation is preceded by a decline in hopelessness among patients with MDD. METHOD: Of the 269 Vantaa Depression Study patients with DSM-IV MDD, 103 patients scored > or = 6 points at baseline on the Scale for Suicidal Ideation (SSI). Seventy of these patients were followed-up weekly either until they scored zero points on the SSI, or up to 26 weeks. RESULTS: The median duration for a decline of suicidal ideation to zero was 2.2 months after baseline. The level of baseline suicidal ideation, depressive symptoms, and the presence of any personality disorder predicted duration of suicidal ideation. A decline in both depression (BDI) and hopelessness (HS) independently predicted a decline in suicidal ideation. LIMITATIONS: Due to study design, we do not know if suicidal ideation relapsed after the first time the patient reached zero score in the SSI. CONCLUSIONS: Among patients with major depressive disorder having suicidal ideation, the decline in suicidal ideation is independently predicted by preceding declines in the levels of both depressive symptoms as well as hopelessness. The findings are consistent with possible causal roles of declines in depression and hopelessness in reversing the suicidal process.

Differences in Axis I and II comorbidity between bipolar I and II disorders and major depressive disorder.

OBJECTIVE: To obtain a comprehensive view of differences in current comorbidity between bipolar I and II disorders (BD) and (unipolar) major depressive disorder (MDD), and Axis I and II comorbidity in BD in secondary-care psychiatric settings. METHOD: The psychiatric comorbidity of 90 bipolar I and 101 bipolar II patients from the Jorvi Bipolar Study and 269 MDD patients from the Vantaa Depression Study were compared. We used DSM-IV criteria assessed by semistructured interviews. Patients were inpatients and outpatients from secondary-care psychiatric units. Comparable information was collected on clinical history, index episode, symptom status, and patient characteristics. RESULTS: Bipolar disorder and MDD differed in prevalences of current comorbid disorders, MDD patients having significantly more Axis I comorbidity (69.1% vs. 57.1%), specifically anxiety disorders (56.5% vs. 44.5%) and cluster A (19.0% vs. 9.9%) and C (31.6% vs. 23.0%) personality disorders. In contrast, BD had more single cluster B personality disorders (30.9% vs. 24.6%). Bipolar I and bipolar II were similar in current overall comorbidity, but the prevalence of comorbidity was strongly associated with the current illness phase. CONCLUSIONS: Major depressive disorder and BD have somewhat different patterns in the prevalences of comorbid disorders at the time of an illness episode, with differences particularly in the prevalences of anxiety and personality disorders. Current illness phase explains differences in psychiatric comorbidity of BD patients better than type of disorder.

The influence of adversity and perceived social support on the outcome of major depressive disorder in subjects with different levels of depressive symptoms.

BACKGROUND: Adverse life events and social support may influence the outcome of major depressive disorder (MDD). We hypothesized that outcome would depend on the level of depressive symptoms present at the outset, with those in partial remission being particularly vulnerable. METHOD: In the Vantaa Depression Study (VDS), patients with DSM-IV MDD were interviewed at baseline, and at 6 and 18 months. Life events were investigated with the Interview for Recent Life Events (IRLE) and social support with the Interview Measure of Social Relationships (IMSR) and the Perceived Social Support Scale - Revised (PSSS-R). The patients were divided into three subgroups at 6 months, those in full remission (n = 68), partial remission (n = 75) or major depressive episode (MDE) (n = 50). The influence of social support and negative life events during the next 12 months on the level of depressive symptoms, measured by the Hamilton Rating Scale for Depression (HAMD), was investigated at endpoint. RESULTS: The severity of life events and perceived social support influenced the outcome of depression overall, even after adjusting for baseline level of depression and neuroticism. In the full remission subgroup, both severity of life events and subjective social support significantly predicted outcome. However, in the partial remission group, only the severity of events, and in the MDE group, the level of social support were significant predictors. CONCLUSIONS: Adverse life events and/or poor perceived social support influence the medium-term outcome of all psychiatric patients with MDD. These factors appear to have the strongest predictive value in the subgroup of patients currently in full remission.

Breakdown of long-range temporal correlations in theta oscillations in patients with major depressive disorder.

Neuroimaging has revealed robust large-scale patterns of high neuronal activity in the human brain in the classical eyes-closed wakeful rest condition, pointing to the presence of a baseline of sustained endogenous processing in the absence of stimulus-driven neuronal activity. This baseline state has been shown to differ in major depressive disorder. More recently, several studies have documented that despite having a complex temporal structure, baseline oscillatory activity is characterized by persistent autocorrelations for tens of seconds that are highly replicable within and across subjects. The functional significance of these long-range temporal correlations has remained unknown. We recorded neuromagnetic activity in patients with a major depressive disorder and in healthy control subjects during eyes-closed wakeful rest and quantified the long-range temporal correlations in the amplitude fluctuations of different frequency bands. We found that temporal correlations in the theta-frequency band (3-7 Hz) were almost absent in the 5-100 s time range in the patients but prominent in the control subjects. The magnitude of temporal correlations over the left temporocentral region predicted the severity of depression in the patients. These data indicate that long-range temporal correlations in theta oscillations are a salient characteristic of the healthy human brain and may have diagnostic potential in psychiatric disorders. We propose a link between the abnormal temporal structure of theta oscillations in the depressive patients and the systems-level impairments of limbic-cortical networks that have been identified in recent anatomical and functional studies of patients with major depressive disorder.