Borderline personality disorder and depression severity predict suicidal outcomes: A six-month prospective cohort study of depression, bipolar depression, and borderline personality disorder.

BACKGROUND: Suicide risk is high in patients with major depressive disorder (MDD), bipolar disorder (BD) and borderline personality disorder (BPD). Whether risk levels of and risk factors for suicidal ideation (SI) and suicide attempts (SA) are similar or different in these disorders remains unclear, as few directly comparative studies exist. The relationship of short-term changes in depression severity and SI is underinvestigated, and might differ across groups, for example, between BPD and non-BPD patients. METHODS: We followed, for 6 months, a cohort of treatment-seeking, major depressive episode (MDE) patients in psychiatric care (original n = 124), stratified into MDE/MDD, MDE/BD and MDE/BPD subcohorts. We examined risks of suicide-related outcomes and their risk factors prospectively. We examined the covariation of SI and depression over time with biweekly online modified Patient Health Questionnaire 9 surveys and analysed this relationship through multi-level modelling. RESULTS: Risk of SA in BPD (22.2%) was higher than non-BPD (4.23%) patients. In regression models, BPD severity was correlated with risk of SA and clinically significant SI. During follow-up, mean depression severity and changes in depression symptoms were associated with SI risk regardless of diagnosis. CONCLUSIONS: Concurrent BPD in depression seems predictive for high risk of SA. Severity of BPD features is relevant for assessing risk of SA and SI in MDE. Changes in depressive symptoms indicate concurrent changes in risk of SI. BPD status at intake can index risk for future SA, whereas depressive symptoms appear a useful continuously monitored risk index.

Finnish Psychotherapy Quality Register: rationale, development, and baseline results.

BACKGROUND: The push to systematically follow treatment outcomes in psychotherapies to improve health care is increasing worldwide. To manage psychotherapeutic services and facilitate tailoring of therapy according to feedback a comprehensive and feasible data system is needed. AIMS: To describe the Finnish Psychotherapy Quality Register (FPQR), a comprehensive database on availability, quality, and outcomes of psychotherapies. METHODS: We describe the development of the FPQR and outcome for outsourced psychotherapies for adults in Helsinki and Uusimaa hospital district (HUS). Symptom severity and functioning are measured with validated measures (e.g. CORE-OM, PHQ-9, OASIS, AUDIT, and SOFAS). Questionnaires on therapeutic alliance, risks, methods, and goals are gathered from patients and psychotherapist. RESULTS: During 2018-2021, the FPQR included baseline data for 7274 unique patients and 336 psychotherapists. Response rate of measures was 85-98%. The use of the register was mandatory for the outsourced therapist of the hospital districts, and the patients were strongly recommended to fulfill the questionnaires. We report outcome for three groups of patients (n = 1844) with final/midterm data. The effect sizes for long psychotherapy (Hedge's g = 0.65 of SOFAS) were smaller than those for short psychotherapy (g = 0.75-0.91). Within three months of referral, 26-60% entered treatment depending on short- or long-term therapy. CONCLUSION: The FPQR forms a novel rich database with commensurate data on availability and outcomes of outsourced psychotherapies. It may serve as a basis for a national comprehensive follow-up system of psychosocial treatments. The Finnish system seems to refer patients with milder symptoms to more intensive treatments and achieve poorer results compared to the IAPT model in UK, Norway, or Australia.

Escitalopram enhances synchrony of brain responses during emotional narratives in patients with major depressive disorder.

One-week treatment with escitalopram decreases amygdala responses to fearful facial expressions in depressed patients, but it remains unknown whether it also modulates processing of complex and freely processed emotional stimuli resembling daily life emotional situations. Inter-subject correlation (ISC) offers a means to track brain activity during complex, dynamic stimuli in a model-free manner. Twenty-nine treatment-seeking patients with major depressive disorder were randomized in a double-blind study design to receive either escitalopram or placebo for one week, after which functional magnetic resonance imaging (fMRI) was performed. During fMRI the participants listened to spoken emotional narratives. Level of ISC between the escitalopram and the placebo group was compared across all the narratives and separately for the episodes with positive and negative valence. Across all the narratives, the escitalopram group had higher ISC in the default mode network of the brain as well as in the fronto-temporal narrative processing regions, whereas lower ISC was seen in the middle temporal cortex, hippocampus and occipital cortex. Escitalopram increased ISC during positive parts of the narratives in the precuneus, medial prefrontal cortex, anterior cingulate and fronto-insular cortex, whereas there was no significant synchronization in brain responses to positive vs negative events in the placebo group. Increased ISC may imply improved emotional synchronization with others, particularly during observation of positive events. Further studies are needed to test whether this contributes to the later therapeutic effect of escitalopram.

Reduced visual contrast suppression during major depressive episodes.

Background: Previous studies have suggested that processing of visual contrast information could be altered in major depressive disorder. To clarify the changes at different levels of the visual hierarchy, we behaviourally measured contrast perception in 2 centre-surround conditions, assessing retinal and cortical processing. Methods: As part of a prospective cohort study, our sample consisted of controls (n = 29; 21 female) and patients with unipolar depression, bipolar disorder and borderline personality disorder who had baseline major depressive episodes (n = 111; 74 female). In a brightness induction test that assessed retinal processing, participants compared the perceived luminance of uniform patches (presented on a computer screen) as the luminance of the backgrounds was varied. In a contrast suppression test that assessed cortical processing, participants compared the perceived contrast of gratings, which were presented with collinearly or orthogonally oriented backgrounds. Results: Brightness induction was similar for patients with major depressive episodes and controls (p = 0.60, d = 0.115, Bayes factor = 3.9), but contrast suppression was significantly lower for patients than for controls (p < 0.006, d = 0.663, Bayes factor = 35.2). We observed no statistically significant associations between contrast suppression and age, sex, or medication or diagnostic subgroup. At follow-up (n = 74), we observed some normalization of contrast perception. Limitations: We assessed contrast perception using behavioural tests instead of electrophysiology. Conclusion: The reduced contrast suppression we observed may have been caused by decreased retinal feedforward or cortical feedback signals. Because we observed intact brightness induction, our results suggest normal retinal but altered cortical processing of visual contrast during a major depressive episode. This alteration is likely to be present in multiple types of depression and to partially normalize upon remission.

Neuropeptide precursor VGF is genetically associated with social anhedonia and underrepresented in the brain of major mental illness: its downregulation by DISC1.

In a large Scottish pedigree, disruption of the gene coding for DISC1 clearly segregates with major depression, schizophrenia and related mental conditions. Thus, study of DISC1 may provide a clue to understand the biology of major mental illness. A neuropeptide precursor VGF has potent antidepressant effects and has been reportedly associated with bipolar disorder. Here we show that DISC1 knockdown leads to a reduction of VGF, in neurons. VGF is also downregulated in the cortices from sporadic cases with major mental disease. A positive correlation of VGF single-nucleotide polymorphisms (SNPs) with social anhedonia was also observed. We now propose that VGF participates in a common pathophysiology of major mental disease.

Proteomic, genomic and translational approaches identify CRMP1 for a role in schizophrenia and its underlying traits.

Schizophrenia is a chronic illness of heterogenous biological origin. We hypothesized that, similar to chronic progressive brain conditions, persistent functional disturbances of neurons would result in disturbed proteostasis in the brains of schizophrenia patients, leading to increased abundance of specific misfolded, insoluble proteins. Identification of such proteins would facilitate the elucidation of molecular processes underlying these devastating conditions. We therefore generated antibodies against pooled insoluble proteome of post-mortem brains from schizophrenia patients in order to identify unique, disease-specific epitopes. We successfully identified such an epitope to be present on collapsin-response mediator protein 1 (CRMP1) in biochemically purified, insoluble brain fractions. A genetic association analysis for the CRMP1 gene in a large Finnish population cohort (n = 4651) corroborated the association of physical and social anhedonia with the CRMP1 locus in a DISC1 (Disrupted-in-schizophrenia 1)-dependent manner. Physical and social anhedonia are heritable traits, present as chronic, negative symptoms of schizophrenia and severe major depression, thus constituting serious vulnerability factors for mental disease. Strikingly, lymphoblastoid cell lines derived from schizophrenia patients mirrored aberrant CRMP1 immunoreactivity by showing an increase of CRMP1 expression, suggesting its potential role as a blood-based diagnostic marker. CRMP1 is a novel candidate protein for schizophrenia traits at the intersection of the reelin and DISC1 pathways that directly and functionally interacts with DISC1. We demonstrate the impact of an interdisciplinary approach where the identification of a disease-associated epitope in post-mortem brains, powered by a genetic association study, is rapidly translated into a potential blood-based diagnostic marker.

How changes in depression severity and borderline personality disorder intensity are linked - a cohort study of depressed patients with and without borderline personality disorder.

BACKGROUND: Borderline personality disorder (BPD) is often complicated by comorbid major depressive episodes (MDEs), which can occur as part of major depressive disorder (MDD) or bipolar disorder (BD). Such comorbidity is related to worse outcomes in both disorders. Subsyndromal features of BPD are also common in depression. However, studies of simultaneous changes in BPD and depression severities are scarce, and their interactions are poorly understood. AIMS: Studying the associations between changes in BPD and depression symptoms over the course of an MDE. METHODS: In a 6-month naturalistic cohort study of MDE/BPD, MDE/MDD, and MDE/BD patients (N = 95), we measured change in BPD features between baseline and six months with the Borderline Personality Disorder Severity Index (BPDSI), an interviewer-rated instrument quantifying recent temporal frequency of BPD symptoms. We examined changes in BPD severity and their correlation with depression severity and other clinical measures and compared these across patient groups. RESULTS: There were significant reductions in BPD severity, both in number of positive BPD criteria (-0.35, sd 1.38, p = 0.01672) and in BPDSI scores (-4.23, SD 6.74, p < 0.001), reflecting mainly a reduction in temporal frequency of symptoms. These were similar in all diagnostic groups. In multivariate regression models, changes in depression severity independently associated with changes in symptoms in the BDSI. This relationship was strongest in MDE/BPD patients but was not found in MDD patients without BPD. CONCLUSIONS: In the six-month follow-up, BPD features in MDE patients alleviated mainly by decreasing temporal symptom frequency and intensity. In BPD patients with comorbid MDE, changes in both conditions are strongly correlated.

Affect dimensions and variability during major depressive episodes: Ecological momentary assessment of unipolar, bipolar, and borderline patients and healthy controls.

Differentiating major depressive episodes (MDEs) of major depressive disorder (MDD), bipolar disorder (MDE/BD) and the MDEs comorbid with borderline personality disorder (MDE/BPD) is crucial for appropriate treatment, and knowledge of phenomenological differences may aid this. However, studies comparing affect experiences of these three patient groups and healthy subjects are scarce. In our study, participants (N = 114), including patients with MDD (n = 34), MDE/BD (n = 27), and MDE/BPD (n = 24), and healthy controls (HC, n = 29) responded to ecological momentary assessment (EMA) with ten circumplex model affect items ten times daily for seven days (7709 recordings). Explorative factor analysis resulted in two affect dimensions. The positive dimension included active, excited, cheerful (high arousal), and content (low arousal) affects, and the negative dimension irritated, angry, and nervous (high arousal) affects. Relative to HC, patients reported 3.5-fold negative affects (mean MDD 1.36 (SD 0.92), MDE/BD 1.43 (0.76), MDE/BPD 1.81 (0.95) vs. HC 0.44 (0.49) (p < 0.01)) but 0.5-fold positive affects (2.01 (0.90), 1.95 (0.89), 2.24 (1.03), vs. 3.2 (0.95), respectively (p < 0.01)). We used multilevel modelling. Negative-affect within-individual stability was lowest in MDE/BPD and highest in MDD. Negative affect predicted concurrent positive affect more in MDE/BPD than in MDD. Moderate size of subcohorts and no inpatients were limitations. Despite apparently similar MDEs, affective experiences may differ between BPD, BD, and MDD patients. Clinical subgroups of patients with depression may vary in affective instability and concurrent presence of negative and positive affects during depression.

A randomized clinical trial of histamine 2 receptor antagonism in treatment-resistant schizophrenia.

Histamine has important functions as regulator of several other key neurotransmitters. Patients with schizophrenia have lower histamine H1 receptor levels. Since a case report in 1990 of an effect of the H2 antagonist famotidine on negative symptoms in schizophrenia, some open-label trials have been performed, but no randomized controlled trial. Recently, it was shown that clozapine is a full inverse agonist at the H2 receptor. We performed a researcher-initiated, academically financed, double-blind, placebo-controlled, parallel-group, randomized trial with the histamine H2 antagonist famotidine in treatment-resistant schizophrenia. Thirty subjects with schizophrenia were randomized to have either famotidine (100 mg twice daily, n = 16) or placebo (n = 14) orally, added to their normal treatment regimen for 4 weeks. They were followed up weekly with the Scale for the Assessment of Negative Symptoms (SANS), the PANSS (Positive and Negative Syndrome Scale), and Clinical Global Impression (CGI) Scale. In the famotidine group, the SANS score was reduced by 5.3 (SD, 13.1) points, whereas in the placebo group the SANS score was virtually unchanged (mean change, +0.2 [SD, 9.5]). The difference did not reach statistical significance (P = 0.134) in Mann-Whitney U analysis. However, the PANSS Total score and the General subscore as well as the CGI showed significantly (P < 0.05) greater change in the famotidine group than in the placebo group. No significant adverse effects were observed. This is the first placebo-controlled, randomized clinical trial showing a beneficial effect of histamine H2 antagonism in schizophrenia. H2 receptor antagonism may provide a new alternative for the treatment of schizophrenia.

Relationship between daily rated depression symptom severity and the retrospective self-report on PHQ-9: A prospective ecological momentary assessment study on 80 psychiatric outpatients.

BACKGROUND: Depression-related negative bias in emotional processing and memory may bias accuracy of recall of temporally distal symptoms. We tested the hypothesis that when responding to the Patient Health Questionnaire (PHQ-9) the responses reflect more accurately temporally proximal than distal mood states. METHODS: Currently, depressed psychiatric outpatients (N = 80) with depression confirmed in semi-structured interviews had the Aware application installed on their smartphones for ecological momentary assessment (EMA). The severity of "low mood", "hopelessness", "low energy", "anhedonia", and "wish to die" was assessed on a Likert scale five times daily during a 12-day period, and thereafter, the PHQ-9 questionnaire was completed. We used auto- and cross-correlation analyses and linear mixed-effects multilevel models (LMM) to investigate the effect of time lag on the association between EMA of depression symptoms and the PHQ-9. RESULTS: Autocorrelations of the EMA of depressive symptom severity at two subsequent days were strong (r varying from 0.7 to 0.9; p < 0.001). "Low mood" was the least and "wish to die" the most temporally stable symptom. The correlations between EMA of depressive symptoms and total scores of the PHQ-9 were temporally stable (r from 0.3 to 0.6; p < 0.001). No effect of assessment time on the association between EMA data and the PHQ-9 emerged in the LMM. LIMITATIONS: Altogether 11.5 % of observations were missing. CONCLUSIONS: Despite fluctuations in severity of some of the depressive symptoms, patients with depression accurately recollect their most dominant symptoms, without a significant recall bias favouring the most recent days, when responding to the PHQ-9.

[Somatic involuntary hospitalization]. / Somaattinen pakkohoito.

In a situation where the patient's own wish concerning her/his somatic treatment cannot be reliably assessed, the attending physician is obliged to treat the patient in the best possible way. Such situations include for instance unconsciousness, confusion and also severe mental disorders, such as psychoses. If the decision making capacity of the patient is lowered and immediate threat to somatic health is present, treatment decisions are made by the physician responsible for somatic care. The patient may be under somatic treatment also during involuntary psychiatric care.

Bipolar disorder predicted shorter and borderline personality disorder symptoms longer time to remission - A prospective cohort study of major depressive patients.

BACKGROUND: Major depressive episodes (MDEs) of major depressive (MDD) or bipolar disorders (BD) are frequently complicated by features of borderline personality disorder (BPD). Mixed features are a hallmark of BD and affective lability of BPD, and both may markedly influence illness course. However, direct comparisons of outcome of depression in MDD, BD, and BPD are scarce. METHODS: In a cohort study based on stratified sampling, we diagnosed psychiatric MDE patients with SCID-I/P and SCID-II interviews and examined mixed symptoms using the Mix-MDE scale and borderline symptoms using the Borderline Personality Disorder Severity Index. During a six-month prospective follow-up, the MDE patients with MDD (n = 39), BD (n = 33), or BPD (n = 23) completed biweekly online assessments. Using life chart methodology, we divided the follow-up period into qualitatively different mood state periods. We investigated durations of mood episodes, times to first full symptomatic remission, and their predictors. RESULTS: Remission rates were similar in MDD, MDE/BD, and MDE/BPD patients. MDE/BD patients experienced more numerous and shorter distinct mood state periods during follow-up than the others. MDE/BD was associated with shorter (HR = 2.44, 95 % CI = 1.27-4.67) and dimensionally assessed BPD severity with longer time to first remission (HR = 0.95, 95 % CI = 0.91-1.00). LIMITATIONS: Moderate sample size and follow-up duration. CONCLUSIONS: Course of illness over six months differs between the three depressive groups. Bipolar depressive patients have the most alternating course and the shortest time to first period of remission. Dimensionally assessed severity of BPD may predict longer time to remission from depression.

Identifying schizophrenia and other psychoses with psychological scales in the general population.

We study the predictive power and associations of several psychopathology and temperament scales with respect to schizophrenia and other psychotic disorders. Measures of psychopathology (Physical and Social Anhedonia Scales, Perceptual Aberration Scale, Hypomanic Personality Scale, Bipolar II Scale, and Schizoidia Scale) and the Temperament and Character Inventory were included in the 31-year follow-up of the prospective Northern Finland 1966 birth cohort (N = 4926). The Perceptual Aberration Scale was the best scale for concurrent validity in psychoses, and also the best psychopathology scale in terms of discriminant validity. Participants scoring high in hypomanic personality were at the highest risk for developing psychosis during the 11-year follow-up. Harm avoidance was a dominant temperament dimension in individuals with psychosis compared with participants without psychiatric diagnoses. These scales are useful as vulnerability markers in studying psychoses.

Presence and Overlap of Bipolar Symptoms and Borderline Features during Major Depressive Episodes.

BACKGROUND: Bipolar symptoms and borderline personality features occur in both unipolar and bipolar major depressive episodes (MDEs). We investigated their prevalence, severity, co-occurrence and overlap. METHODS: We interviewed 124 psychiatric outpatients with MDE using the Structured Clinical Interview for DSM-IV-TR Axis I and II Disorders, the Borderline Personality Disorder Severity Index (BPDSI-IV), and about past (hypo)manic episodes, and stratified them according to the principal diagnosis into subcohorts of major depressive disorder (MDD, n = 50), bipolar disorder (BD, n = 43), and borderline personality disorder (BPD, n = 31). We quantified (hypo)manic symptoms using a novel semi-structured interview (MIXed symptoms during MDE, MIX-MDE) with good psychometric qualities. RESULTS: The subcohorts did not differ in MDE severity. They differed significantly in some (hypo)manic symptoms being present on most days in 24% of MDD, 30% of BD, and 42% of BPD subcohort, but only 5% of the BD subcohort fulfilled the DSM-5 mixed features. The mean MIX-MDE scores were 5.7 (SD 4.0), 12.0 (8.2) and 10.5 (7.5), and BPDSI-IV scores 15.6 (7.0), 17.2 (6.2) and 26.9 (8.7), respectively (both p < 0.001). (Hypo)manic days and unspecific symptoms of distractibility and irritability inflated the correlation of observed (hypo)manic symptoms and borderline features. LIMITATIONS: Moderate sample size, limited age variation (18-50 years); no previous validation of MIX-MDE. CONCLUSIONS: Presence of some mixed and borderline features is common in MDEs, with overlap and diagnosis-specific differences. Unspecific symptoms of irritability and distractibility and the aggravating impact of hypomania on perceived BPD features blur the differential diagnosis.

Data on schizotypy and affective scales are gender and education dependent--study in the Northern Finland 1966 Birth Cohort.

We present psychometric properties and normative data by gender and educational level in scales related to schizotypy and affective disorders in a large population-based adult sample. As part of the 31-year follow-up survey of the Northern Finland 1966 Birth Cohort; Bipolar II scale (BIP2), Hypomanic Personality Scale (HPS), Physical Anhedonia Scale (PAS), Social Anhedonia Scale (SAS), Perceptual Aberration Scale (PER) and Schizoidia Scale (SCHD) were filled in by 4928 subjects. In total sample mean scores were: BIP2 10.59 (3.80), HPS 11.26 (7.03), PAS 14.99 (S.D. 7.03), SAS 9.44 (5.52), PER 2.35 (3.26) and SCHD 2.56 (1.42). Men scored higher (had more psychopathological symptoms) in PAS and SAS (P<0.001), and in BIP2 (P=0.02). Women had higher scores in SCHD, HPS and PER (P<0.001). Participants with a lower level of education scored higher in all scales; differences were largest in BIP2, PAS and SAS (ES>0.5,P<0.001). The gender and education differences were moderate or large in all the included scales. These differences should be taken into account when considering normal values in these scales. The findings indicate that commonly used student samples are likely to be biased when compared to community based samples.

Borderline Personality Disorder With Depression Confers Significant Risk of Suicidal Behavior in Mood Disorder Patients-A Comparative Study.

OBJECTIVE: We investigated risk factors for suicidal ideation and behavior among currently depressed patients with major depressive disorder (MDD), major depressive episode (MDE) in bipolar disorder (BD), or MDE with comorbid borderline personality disorder (MDE/BPD). We compared current and lifetime prevalence of suicidal ideation and behavior, and investigated dimensional measures of BPD or mixed affective features of the MDE as indicators of risk. METHODS: Based on screening of 1,655 referrals, we recruited 124 psychiatric secondary care outpatients with MDE and stratified them into three subcohorts (MDD, BD, and MDE/BPD) using the Structured Clinical Interview for DSM-IV I and II. We examined suicidal ideation and behavior with the Columbia Suicide Severity Rating Scale (CSSRS). In addition, we quantified the severity of BPD symptoms and BD mixed features both categorically/diagnostically and dimensionally (using instruments such as the Borderline Personality Disorder Severity Index) in two time frames. RESULTS: There were highly significant differences between the lifetime prevalences of suicide attempts between the subcohorts, with attempts reported by 16% of the MDD, 30% of the BD, and 60% of the BPD subcohort. Remarkably, the lifetime prevalence of suicide attempts in patients with comorbid BD and BPD exceeded 90%. The severity of BPD features was independently associated with risk of suicide attempts both lifetime and during the current MDE. It also associated in a dose-dependent manner with recent severity of ideation in both BPD and non-BPD patients. In multinominal logistic regression models, hopelessness was the most consistent independent risk factor for severe suicidal ideation in both time frames, whereas younger age and more severe BPD features were most consistently associated with suicide attempts. CONCLUSIONS: Among patients with major depressive episodes, diagnosis of bipolar disorder, or presence of comorbid borderline personality features both imply remarkably high risk of suicide attempts. Risk factors for suicidal ideation and suicidal acts overlap, but may not be identical. The estimated severity of borderline personality features seems to associate with history of suicidal behavior and current severity of suicidal ideation in dose-dependent fashion among all mood disorder patients. Therefore, reliable assessment of borderline features may advance the evaluation of suicide risk.

Impact of the dopamine receptor gene family on temperament traits in a population-based birth cohort.

Although the genetic determinants of personality have been intensively investigated especially since Cloninger proposed his psychobiological model of temperament and character, findings to date remain inconclusive and very few studies have addressed the topic in large population cohorts. In the current study we investigated one gene family in its entirety by addressing the role of all known dopamine receptor genes, DRD1-DRD5, on Cloninger's temperament traits in a Finnish population-based birth cohort. The study sample (n = 1,434) was ascertained from the Northern Finland Birth Cohort 1966 with over 5,000 study individuals tested at the age of 31 years. We utilized the genetic homogeneity and genealogical structure of this population to uncover putative effects of these genes on temperament traits at the population level. Our strategy utilizing a large birth cohort and its well established genealogical structure represents an optimal design for studying normally distributed traits. We also wished to provide a comprehensive view to one biologically relevant gene family instead of testing single candidate genes. We report evidence of association of several SNPs at the 5' end of dopamine receptor D2 (DRD2) with Novelty seeking (low) and Harm avoidance (high), and at the 3' end of DRD2 with Persistence. The strongest evidence of association emerged from females. Our study supports the involvement of the dopamine pathway in temperament traits, in particular underlining the role of DRD2 in Novelty seeking, Harm avoidance and Persistence.

Temperament profiles in personality disorders among a young adult population.

The objective of this study was to describe the temperament dimension profiles assessed by the Temperament and Character Inventory (TCI) among young adults with the DSM-III-R personality disorder (PD). Our hypothesis was that PD clusters and separate PDs can be distinguished from one another by their specific temperament profiles. As a part of the 31-year follow-up survey of the prospective Northern Finland 1966 Birth Cohort, the cohort members living in the city of Oulu at the age of 31 years (n=1609) were invited to participate in a two-phase field study. The Structured Clinical Interview for DSM-III-R for PDs (SCID-II) was used as diagnostic instrument. The final study sample consisted of the 1311 subjects who had completed the Hopkins Symptom Check List-25 questionnaire for screening and had given a written informed consent. Of the 321 SCID interviewed subjects, 74 met the criteria for at least one PD and had completed the TCI. The mean TCI scores of subjects with PD and control subjects without PD (n=910) were compared. Low Novelty Seeking, high Harm Avoidance and low Reward Dependence characterized cluster A and C PDs. Subjects with a cluster B PD did not differ from controls, except for Novelty Seeking, which was high. The temperament dimensions could not distinguish different PDs very well, with the only exception of persons with obsessive-compulsive PD. PD clusters were associated with different profiles of temperament, lending some support for Cloninger's typology.

Short-term escitalopram treatment normalizes aberrant self-referential processing in major depressive disorder.

BACKGROUND: Increased self-focus and negative self-concept play an important role in depression. Antidepressants influence self-referential processing in healthy volunteers, but their function in self-processing of depressed patients remains unknown. METHODS: Thirty-two depressed patients were randomly allocated to receive either escitalopram 10 mg or placebo for one week. After one week, neural responses to positive and negative self-referential adjectives and neutral control stimuli were assessed with functional magnetic resonance imaging. A group of matched healthy volunteers served as a control group. RESULTS: Escitalopram decreased responses of medial fronto-parietal regions to self-referential words relative to non-emotional control stimuli, driven by increased responses to the control condition. Escitalopram also increased responses in the pre-defined region of the medial prefrontal cortex (MPFC) and the anterior cingulate cortex (ACC) to positive relative to negative words. Importantly, the changes in neural responses occurred before any effect on depressive symptoms, implying a direct effect of escitalopram. Furthermore, the placebo group had decreased responses of the MPFC and the ACC to positive self-referential processing relative to the matched healthy controls. However, neural responses of the escitalopram group and the healthy unmedicated controls were similar. LIMITATIONS: Differences between the groups in self-reported depression symptoms and personality traits may have influenced the results. CONCLUSION: One-week treatment with escitalopram normalized aberrant self-referential processing in depressed patients, shifting the focus from the self to the external environment and potentiating positive self-referential processing. This may be an important factor in mechanism of action of antidepressants.

In vivo DA D(1) receptor selectivity of NNC 112 and SCH 23390.

PURPOSE: [(11)C]NNC 112 and [(11)C]SCH 23390 are selective positron emission tomography (PET) tracers for visualizing dopamine D(1) receptors. It is known that both have some affinity for serotonin 2A receptors, but previous studies have suggested this is negligible compared to D(1) affinity. We sought to verify this property in vivo. PROCEDURES: Two baboons were scanned to measure the selectivity of both tracers with a displacement paradigm. Four baboons were scanned to directly assess [(11)C] NNC 112 affinity for both receptors. RESULTS: In vivo, D(1) to 5-HT(2A) selectivity is six to fourteenfold, not 100-fold as previously reported by other investigators. CONCLUSION: We conclude that about 1/4 of the cortical signal of both [(11)C]NNC 112 and [(11)C]SCH 23390 is due to binding to 5-HT(2A) receptors. If confirmed in humans, this suggests caution should be exercised when drawing conclusions from studies using either tracer. These results also indicate the need for more selective tracers for the D(1) receptor.