Diagnostic conversion from unipolar depression to bipolar disorder, schizophrenia, or schizoaffective disorder: A nationwide prospective 15-year register study on 43 495 inpatients.

OBJECTIVE: To examine temporal patterns and predictors for diagnostic conversion from unipolar depression (UD) to bipolar disorder (BD), schizophrenia, and schizoaffective disorder (SAD). METHODS: A prospective nationwide register-based cohort (n = 43 495) of all first psychiatric hospitalizations due to UD during 1996-2011 was followed up to 15 years. We used cumulative incidence function (CIF) analyses and the Fine-Gray subdistribution model to define the cumulative incidence of the conversions and subdistribution hazard ratios (SHRs) for predictors. RESULTS: The overall 15-year cumulative incidence of conversion was 11.1% (95% CI 10.7-11.6): 7.4% (95% CI 7.0-7.8) for BD, 2.5% (95% CI 2.3-2.7) for schizophrenia, and 1.3% (95% CI 1.1-1.4) for SAD. The highest crude incidence rate emerged during the first year. Psychotic depression predicted higher conversion risk to BD (SHR = 2.0, 95% CI 1.5-2.7), schizophrenia (SHR = 5.3, 95% CI 3.3-8.7), and SAD (SHR = 10.6, 95% CI 4.0-28.4) than mild depression. Female sex, greater overall disturbance, and comorbid personality disorder predicted conversion to BD, whereas young age and male sex to psychotic disorders. CONCLUSIONS: Among patients with first hospitalization due to UD, approximately one in nine converts to another major psychiatric disorder during 15 years, with the highest risk occurring within the first year. Patients with psychotic depression are particularly vulnerable for conversion to other major psychiatric disorders. Conversion to psychotic disorders occurs earlier than to BD. Males are at higher risk for progression to psychotic disorders, whereas females, patients with recurrent depressive episodes, severe disturbance of overall functioning, and personality disorder are at higher risk for converting to BD.

Cause-specific mortality in treatment-resistant major depression: Population-based cohort study.

BACKGROUND: Limited evidence-base on long-term prognosis of treatment-resistant major depression (TRD) is a barrier to clinical decision-making. Therefore, the purpose of this study was to establish cause-specific mortality in TRD compared to non-TRD major depression. METHOD: We identified all individuals with a diagnosis of major depression (MDD) who were treated with an antidepressant aged 15 to 65 years during 2004-2016 in Finland. Persons with over two treatment trials were defined to have TRD. Data were analysed with Cox proportional hazard models. RESULTS: 176,942 individuals with MDD (63 % women, median age at index diagnosis 40 years), of whom 11 % (n = 19,305) fulfilled the TRD criteria, were followed-up for 1,525,646 person-years (median 8.9 years). There were 959 deaths (6.1 deaths/1000 person-years) in TRD and 7662 deaths (5.6/1000 person-years) in non-TRD. All-cause mortality was 17 % higher (adjusted hazard ratio (aHR), 1.17; 95 % confidence interval (CI), 1.09-1.25) in TRD compared to non-TRD, when sex and age at index antidepressant prescription were controlled for. In TRD, increased mortality was observed for suicides (aHR, 1.90; 95%CI, 1.64-2.20) and for accidental poisonings (aHR, 1.81; 95%CI, 1.48-2.22), but not for natural causes (aHR, 0.98; 95%CI, 0.90-1.07). A higher proportion of accidental drug overdoses was observed in TRD than in non-TRD (62 % vs 42 %, respectively). LIMITATIONS: Definition of TRD lacks consensus. We used routine data to define TRD. CONCLUSIONS: The markedly increased mortality due to suicides and accidental overdoses suggests that persons with TRD may experience higher intensity symptoms and more severe suicidal ideation than persons with non-TRD major depression.

Psychosocial outcome in patients at clinical high risk of psychosis: a prospective follow-up.

PURPOSE: In patients at clinical high risk (CHR) of psychosis, transition to psychosis has been the focus of recent studies. Their broader outcome has received less attention. We studied psychosocial state and outcome in CHR patients. METHODS: In the European Prediction of Psychosis Study, 244 young help-seeking CHR patients were assessed with the Strauss and Carpenter Prognostic Scale (SCPS) at baseline, and 149 (61.1%) of them were assessed for the second time at the 18-month follow-up. The followed patients were classified into poor and good outcome groups. RESULTS: Female gender, ever-married/cohabitating relationship, and good working/studying situation were associated with good baseline SCPS scores. During follow-up, patients' SCPS scores improved significantly. Good follow-up SCPS scores were predicted by higher level of education, good working/studying status at baseline, and white ethnicity. One-third of the followed CHR patients had poor global outcome. Poor working/studying situation and lower level of education were associated with poor global outcome. Transition to psychosis was associated with baseline, but not with follow-up SCPS scores or with global outcome. CONCLUSION: The majority of CHR patients experience good short-term recovery, but one-third have poor psychosocial outcome. Good working situation is the major indicator of good outcome, while low level of education and non-white ethnicity seem to be associated with poor outcome. Transition to psychosis has little effect on psychosocial outcome in CHR patients. In treating CHR patients, clinicians should focus their attention on a broader outcome, and not only on preventing transition to psychosis.

Seasonal Effects on Hospitalizations Due to Mood and Psychotic Disorders: A Nationwide 31-Year Register Study.

Purpose: To examine seasonal patterns of hospital admissions due to mood and psychotic disorders and to investigate whether the admission rates show variation according to the seasonal daylength (photoperiods). Patients and Methods: A retrospective nationwide register-based cohort of all psychiatric admissions (N=978,079) during 1987-2017 in Finland was utilized. The smoothed time-series of adjusted ratio of observed and expected (O/E) daily counts were estimated to examine seasonal variation. The mean O/E with 95% confidence intervals (CI) was used to study the admission rates by photoperiods. The calendar days were classified into the 71-day photoperiods based on the daylength (long/summer, short/winter, equal/spring, equal/fall) and the pace of change in daylength (slowly/rapidly increasing/decreasing daylength). Results: Manic episodes peaked in summer during the long (mean O/E=1.10, 95% CI=1.06-1.13) and slowly decreasing (1.09, 1.06-1.13) photoperiods and had a nadir in winter during the slowly increasing (0.93, 0.89-0.98) photoperiod. Admissions for unipolar depressive (UPD) episodes peaked in autumn and in spring at the end of the rapidly decreasing (1.03, 1.02-1.04) and increasing (1.03, 1.01-1.04) photoperiod, and dropped in summer during the long and slowly decreasing (0.95, 0.94-0.96) photoperiods. Bipolar depressive (BPD) and mixed episodes signaled excess admissions in autumn and in spring. Admissions for schizophrenia were higher than expected from summer to early-autumn, during the long and slowly decreasing photoperiods (1.02, 1.02-1.03), and lower than expected in other seasons, especially in mid-spring during the rapidly increasing photoperiod (0.98, 0.98-0.99). Conclusion: The study indicates the seasonality and photoperiodicity of mental disorders, especially for manic episodes. The seasonal pattern is similar between schizophrenia and manic episodes, and between UPD, BPD, and mixed episodes.

Differentiating adolescents at clinical high risk for psychosis from psychotic and non-psychotic patients with the Rorschach.

This study was designed to assess cognitive functioning in a clinical sample of adolescents with heterogeneous psychiatric diagnoses, with a specific focus on patients at clinical high risk (CHR) for psychosis. The sample comprised 22 patients identified at CHR for psychosis, 67 psychotic and 187 non-psychotic, non-CHR patients. Neuropsychological assessment was conducted as part of the clinical examination and treatment, including Wechsler Intelligence Scale for Children (WISC)-III and/or Wechsler Adult Intelligence Scale (WAIS)-III measures of verbal comprehension, perceptual organisation, working memory and processing speed, Wisconsin Card Sorting Test (WCST) measures of executive function, and the Rorschach Comprehensive System measures of perceptual and thinking accuracy. Patients at CHR for psychosis did not significantly differ from other patient groups in terms of intellectual or executive functions. The Rorschach Perceptual Thinking Index (PTI) distinguished patients at CHR for psychosis from those diagnosed as having non-psychotic disorders, but not from those diagnosed as psychotic. Our results suggest perceptual and thought disturbance as an important indicator of vulnerability to psychosis.

Perceived negative attitude of others as an early sign of psychosis.

AIM: Risk of psychosis is defined by the presence of positive psychotic-like symptoms, by subtle self-perceived cognitive and perceptual deficiencies, or by decreased functioning with familial risk of psychosis. We studied the associations of psychiatric outpatients' self-reported functioning and interpersonal relationships with vulnerability to and risk of psychosis. METHODS: A total of 790 young patients attending psychiatric outpatient care completed the PROD screen [Heinimaa M, Salokangas RKR, Ristkari T, Plathin M, Huttunen J, Ilonen T, et al. PROD-screen - a screen for prodromal symptoms of psychosis. Int J Meth Psychiatr Res 2003;12:92-04.], including questions on functioning, interpersonal relationships and subtle specific (psychotic-like) and non-specific symptoms. Vulnerability to psychosis was assessed employing the patient's written descriptions of specific symptoms. Of the patients vulnerable to psychosis, those at current risk of psychosis were assessed using the Bonn Scale for Assessment of Basic Symptoms [Schultze-Lutter F, Klosterkötter J. Bonn scale for assessment of basic symptoms - prediction list, BSABS-P. Cologne: University of Cologne; 2002] and the Structured Interview for Positive symptoms [Miller TJ, McGlashan TH, Rosen JL, Somjee L, Markovich PJ, Stein K, et al. Prospective diagnosis of the initial prodrome for schizophrenia based on the structured interview for prodromal syndromes: preliminary evidence of interrater reliability and predictive validity. Am J Psychiatry 2002;159:863-65.]. RESULTS: In all, 219 patients vulnerable to and 55 patients at current risk of psychosis were identified. Vulnerability to psychosis was associated with all items of functioning and interpersonal relationships. Current risk of psychosis, however, was associated only with the subjectively reported negative attitude of others. Negative attitude of others was also associated with feelings of reference at both vulnerability and risk levels. CONCLUSION: The subjective experience of negative attitude of others towards oneself may be an early indicator of psychotic development.

Axis-I disorders and vulnerability to psychosis.

BACKGROUND: The psychopathology that manifests during the prodromal phase of first-episode psychosis is varied. Little is known about the clinical diagnoses of subjects with so-called prodromal or psychotic-like symptoms. METHOD: Samples of psychotic patients, first-degree relatives (FDRs) of psychotic, or severely ill patients, treatment-seeking patients, and a random community sample (in all 157 subjects) were assessed by the Structured Interview for Prodromal Symptoms (SIPS) and the SCID-I. Vulnerability to psychosis (VTP) was defined by severity of positive symptoms reported in the SIPS interview and associated with lifetime SCID-I diagnoses. RESULTS: The number of lifetime diagnoses received increased linearly as the SIPS symptoms approached more psychotic-like phenomena. All VTP subjects received on average 2.5, and currently prodromal subjects 2.9 lifetime SCID-I diagnoses, while the corresponding figure for non-VTP subjects was 0.7 (p<0.0001). Mood disorders and comorbid anxiety disorders were particularly common. CONCLUSION: Vulnerability to psychosis seems to be associated with a high number of lifetime Axis-I diagnoses. Occurrence of anxiety disorders is remarkable, and most VTP subjects can be diagnosed with a lifetime mood disorder. VTP subjects require careful assessment of mood and anxiety symptoms and adequate treatment for their multiple disorders.

Axis I diagnoses and transition to psychosis in clinical high-risk patients EPOS project: prospective follow-up of 245 clinical high-risk outpatients in four countries.

BACKGROUND: In selected samples, a considerable number of patients at clinical high risk of psychosis (CHR) are found to meet criteria for co-morbid clinical psychiatric disorders. It is not known how clinical diagnoses correspond to or even predict transitions to psychosis (TTP). Our aim was to examine distributions of life-time and current Axis I diagnoses, and their association with TTP in CHR patients. METHODS: In the EPOS (European Prediction of Psychosis Study) project, six European outpatient centres in four countries examined 245 young help-seeking patients, who fulfilled the inclusion criteria for clinical risk of psychosis according to the Structured Interview for Prodromal Syndromes (SIPS 3.0) or the Bonn Scale for the Assessment of Basic Symptoms - Prediction List basic symptoms (BASBS-P). Patients who had experienced a psychotic episode lasting more than one week were excluded. Baseline and life-time diagnoses were assessed by the Structured Clinical Interview for DSM-IV (SCID-I). TTP was defined by continuation of BLIPS for more than seven days and predicted in Cox-regression analysis. RESULTS: Altogether, 71% of the CHR patients had one or more life-time and 62% one or more current SCID-I diagnosis; about a half in each category received a diagnosis of life-time depressive and anxiety disorder. Currently, 34% suffered from depressive and 39% from anxiety disorder. Four percent received a current SCID diagnosis of bipolar, and 6.5% of somatoform disorder. During follow-up, 37 (15.1%) patients had developed full-blown psychosis. In bivariate analyses, current non-psychotic bipolar disorder associated significantly with TTP. In multivariate analyses, current bipolar disorder, somatoform and unipolar depressive disorders associated positively, and anxiety disorders negatively, with TTP. CONCLUSIONS: Both life-time and current mood and anxiety disorders are highly prevalent among clinical help-seeking CHR patients and need to be carefully evaluated. Among CHR patients, occurrence of bipolar, somatoform and depressive disorders seems to predict TTP, while occurrence of anxiety disorder may predict non-transition to psychosis.

Striatal dopamine synthesis in first-degree relatives of patients with schizophrenia.

BACKGROUND: First degree relatives (FDR) of patients with schizophrenia have higher risk of developing schizophrenia than the general population. Previous positron emission tomography (PET) studies have shown that striatal presynaptic dopamine synthesis capacity is increased in schizophrenia. We investigated whether this same phenomenon is shared by individuals with increased genetic risk for schizophrenia. METHODS: We used 6-[18F]-fluorodopa (FDOPA) PET imaging to measure striatal dopamine synthesis capacity. We studied 17 nonpsychotic subjects with an FDR with schizophrenia. This group was compared to 17 healthy subjects with no FDRs with schizophrenia. RESULTS: A conventional region of interest (ROI)-analysis indicated that FDOPA uptake (K(i)) in the caudate-putamen was statistically significantly higher in the FDR group than in the control group. A voxel-level analysis confirmed these results. CONCLUSIONS: These results suggest that the changes of striatal presynaptic dopamine synthesis seen previously in neuroleptic-naive schizophrenic patients is also present in FDRs of patients with schizophrenia. These findings have implications for the early detection of psychosis as well as for pharmacological interventions in individuals at risk for psychosis.

Quality of life and functioning ability in subjects vulnerable to psychosis.

BACKGROUND: It is well established that quality of life (QOL) and functioning ability are impaired in psychosis, especially schizophrenia. Little is known about QOL and functioning in subjects vulnerable to psychosis (VTP). METHOD: Three samples of nonpsychotic subjects (first-degree relatives of psychotic or severely ill patients, treatment-seeking patients, and a random community sample, in all 133 subjects) were assessed by the Structured Interview for Prodromal Symptoms and their vulnerability to psychosis was defined by severity of lifetime psychotic-like positive symptoms (nonsymptomatic, symptomatic, VTP). Quality of life was assessed by the Heinrichs' Quality of Life Scale and the Global Assessment of Functioning Ability (GAF) was used to measure functioning. Variance of QOL and GAF was explained by vulnerability status and psychiatric symptoms. RESULTS: Quality of life and functioning ability decreased linearly as positive symptom intensity increased and was lowest in the VTP subjects when background factors were controlled for. In multivariate analysis, negative symptoms predicted low QOL/GAF scores in addition to vulnerability status that was based on positive symptoms. CONCLUSION: Vulnerability to psychosis is associated with decreased QOL and impaired functioning ability. Although current diagnostic evaluation of patients at high risk of psychosis relies heavily on the occurrence of positive symptoms, negative symptoms seem to be strongly associated with QOL and functioning ability in VTP subjects. This should be taken into account when assessing putatively vulnerable patients and planning treatment interventions for them.

Substance abuse and related diagnoses in early psychosis.

Substance abuse seems to be common among those with early signs of evolving psychosis. This article seeks to determine the prevalence of substance abuse and substance use disorders (SUDs) and the association of abuse and SUD with vulnerability psychosis among a sample of first-degree relatives of schizophrenic patients (n = 70), help-seekers (n = 29), and control subjects (n = 34). The Structured Interview for Prodromal Symptoms (SIPS) 1.0 was used to define the vulnerability status and the Structured Clinical Interview for DSM-IV Axis I to diagnose the subjects. Data on various other measures, including premorbid adjustment, personality disorder symptoms, psychological distress, and abuse of substances, were collected. Those who were identified as vulnerable to psychosis reported significantly more lifetime alcohol abuse and had more commonly an SUD than controls. Substance use disorder, as well as alcohol and drug abuse, correlated significantly with personality disorder symptoms and current positive SIPS score and both types of abuse also with disorganization SIPS score. The odds ratio for having an SUD among those vulnerable to psychosis was 6.33 (95% confidence interval, 1.77-22.73). Early psychosis and substance abuse frequently occur together.