Mood-incongruent Psychotic Features Research Articles

Psychotic features, particularly mood incongruence, as a hallmark of severity of bipolar I disorder

BackgroundThe occurrence of psychotic features within mood episodes in patients with bipolar I disorder (BD I) has been associated in some studies with a more severe clinical and socio-professional profile. In contrast, other studies establishing the associations of psychotic features in BD I, and in particular of mood-congruent (MC) and mood-incongruent (MI) features, with clinical characteristics have yielded contradictory results. However, many pre-existing studies have been affected by serious methodological limitations. Using a sample of thoroughly assessed patients with BD I our aims were to: (1) establish the proportion of those with MI and MC features, and (2) compare BD I patients with and without psychotic features as well as those with MI to those with MC features on a wide array of socio-demographic and clinical characteristics including course, psychiatric comorbidity and treatment.MethodsA sample of 162 treated patients with BD I (60.5% female, mean age = 41.4 (s.d: 10.2) years) was recruited within a large family study of mood disorders. Clinical, course and treatment characteristics relied on information elicited through direct diagnostic interviews, family history reports and medical records.Results(1) A total of 96 patients (59.3%) had experienced psychotic features over their lifetime. Among them, 44.8% revealed MI features at least once in their lives. (2) Patients with psychotic features were much less likely to be professionally active, revealed alcohol abuse more frequently and used health care, particularly inpatient treatment, more frequently than those without psychotic features. Within patients with psychotic symptoms, those with MI features showed more clinical severity in terms of a higher likelihood of reporting hallucinations, suicidal attempts and comorbid cannabis dependence.ConclusionOur data provide additional support for both the distinction between BD-I with and without psychotic features as well as the distinction between MI and MC psychotic features. The more severe course of patients with psychotic features, and particularly those with MI psychotic features, highlights the need for thorough psychopathological evaluations to assess the presence of these symptoms to install appropriate treatment.

Abstract- Poster

Background:Lithium continues to be one of first-line prophylactic agents for bipolar disorder (BD) but only about one-third of patients are excellent responders. Studies have described various clinical correlates of treatment response but Indian literature is limited.Aim:to assess the relationship of clinical variables to lithium response in subjects with BD on long-term prophylaxisMethodology:This was a cross-sectional, observational study of 40 subjects, aged 18-60 years, with DSM-5 BD type I, currently in remission. Subjects were included if they were on regular and long-term lithium for atleast one year or more. All subjects were screened using MINI 7.0 to exclude co morbidities and standard scales (YMRS≤4, HAM-D<8) to establish euthymia. Subjects were assessed using clinical proforma, NIMH Life Chart Method, Alda Lithium Response Scale (LRS) and IGSLI scale for typical/atypical features.Results:Mean age for sample was 38.28 ±10.41 years (72.5% males). Mean illness duration was 13.84±9.23 years, with average onset at 24.40±8.21 years. Mean duration on lithium was 5.49±4.11 years (1-18 years) The LRS total (A-B) score showed a significant positive correlation to IGSLI typical features score (p=0.003), time since remission (p=0.034) and a significant negative correlation to IGSLI atypical features score (p=0.019) and age of onset of BD (p=0.037). There was a trend towards poorer lithium response with higher BMI (p=0.052)Conclusion:The clinical course characterized by an early age of onset and more atypical features (via. more manic than depressive episodes, presence of residual symptoms, mood incongruent psychotic features) appear to respond poorer to lithium.

Abstract- Poster

Background:Lithium continues to be one of first-line prophylactic agents for bipolar disorder (BD) but only about one-third of patients are excellent responders. Studies have described various clinical correlates of treatment response but Indian literature is limited.Aim:to assess the relationship of clinical variables to lithium response in subjects with BD on long-term prophylaxisMethodology:This was a cross-sectional, observational study of 40 subjects, aged 18-60 years, with DSM-5 BD type I, currently in remission. Subjects were included if they were on regular and long-term lithium for atleast one year or more. All subjects were screened using MINI 7.0 to exclude co morbidities and standard scales (YMRS≤4, HAM-D<8) to establish euthymia. Subjects were assessed using clinical proforma, NIMH Life Chart Method, Alda Lithium Response Scale (LRS) and IGSLI scale for typical/atypical features.Results:Mean age for sample was 38.28 ±10.41 years (72.5% males). Mean illness duration was 13.84±9.23 years, with average onset at 24.40±8.21 years. Mean duration on lithium was 5.49±4.11 years (1-18 years) The LRS total (A-B) score showed a significant positive correlation to IGSLI typical features score (p=0.003), time since remission (p=0.034) and a significant negative correlation to IGSLI atypical features score (p=0.019) and age of onset of BD (p=0.037). There was a trend towards poorer lithium response with higher BMI (p=0.052)Conclusion:The clinical course characterized by an early age of onset and more atypical features (via. more manic than depressive episodes, presence of residual symptoms, mood incongruent psychotic features) appear to respond poorer to lithium.

Characteristics of mood-congruent and mood-incongruent psychotic features in bipolar disorder

Characteristics of mood-congruent and mood-incongruent psychotic features in bipolar disorder

Association Between Schizophrenia-Related Polygenic Liability and the Occurrence and Level of Mood-Incongruent Psychotic Symptoms in Bipolar Disorder

Bipolar disorder (BD) overlaps schizophrenia in its clinical presentation and genetic liability. Alternative approaches to patient stratification beyond current diagnostic categories are needed to understand the underlying disease processes and mechanisms. To investigate the association between common-variant liability for schizophrenia, indexed by polygenic risk scores (PRSs), and psychotic presentations of BD. This case-control study in the United Kingdom used multinomial logistic regression to estimate differential PRS associations across categories of cases and controls. Participants included in the final analyses were 4436 cases of BD from the Bipolar Disorder Research Network. These cases were compared with the genotypic data for 4976 cases of schizophrenia and 9012 controls from the Type 1 Diabetes Genetics Consortium study and the Generation Scotland study. Data were collected between January 1, 2000, and December 31, 2013. Data analysis was conducted from March 1, 2016, to February 28, 2017. Standardized PRSs, calculated using alleles with an association threshold of P < .05 in the second Psychiatric Genomics Consortium genome-wide association study of schizophrenia, were adjusted for the first 10 population principal components and genotyping platforms. Multinomial logit models estimated PRS associations with BD stratified by Research Diagnostic Criteria subtypes of BD, by lifetime occurrence of psychosis, and by lifetime mood-incongruent psychotic features. Ordinal logistic regression examined PRS associations across levels of mood incongruence. Ratings were derived from the Schedules for Clinical Assessment in Neuropsychiatry interview and the Bipolar Affective Disorder Dimension Scale. Of the 4436 cases of BD, 2966 (67%) were female patients, and the mean (SD) age at interview was 46 [12] years. Across clinical phenotypes, there was an exposure-response gradient, with the strongest PRS association for schizophrenia (risk ratio [RR] = 1.94; 95% CI, 1.86-2.01), followed by schizoaffective BD (RR = 1.37; 95% CI, 1.22-1.54), bipolar I disorder subtype (RR = 1.30; 95% CI, 1.24-1.36), and bipolar II disorder subtype (RR = 1.04; 95% CI, 0.97-1.11). Within BD cases, there was an effect gradient, indexed by the nature of psychosis. Prominent mood-incongruent psychotic features had the strongest association (RR = 1.46; 95% CI, 1.36-1.57), followed by mood-congruent psychosis (RR = 1.24; 95% CI, 1.17-1.33) and BD with no history of psychosis (RR = 1.09; 95% CI, 1.04-1.15). For the first time to date, a study shows a polygenic-risk gradient across schizophrenia and BD, indexed by the occurrence and level of mood-incongruent psychotic symptoms.

Early End to Substance Use Linked to Better Outcome in First-Episode Psychosis

Back to table of contents Previous article Next article Clinical and Research NewsFull AccessEarly End to Substance Use Linked to Better Outcome in First-Episode PsychosisMark MoranMark MoranSearch for more papers by this authorPublished Online:16 Mar 2017https://doi.org/10.1176/appi.pn.2017.3b14AbstractBoth episodic and persistent users had lower rates of symptom remission than nonusers. Persistent users also had more negative symptoms than those who stopped using.Patients experiencing a first-episode psychosis who stop using drugs or alcohol within two years of diagnosis have outcomes similar to those who have never used substances, with fewer symptoms than patients who continued using substances. That’s the finding from a long-term longitudinal study of first-episode patients published last month in Schizophrenia Bulletin. Substance use has been associated with poorer outcomes, including more severe psychopathology, higher relapse rates, and lower life expectancy. While previous studies have suggested discontinuing substance use early in the course of illness can improve symptoms and function, most of these were short-term trials.The new study tracked the relationship between substance use, early abstinence, and psychosis longitudinally over 10 years and suggests the detrimental effects of substance use on mental health may be all but entirely reversed if the person quits early.“The fact that harm can be substantially minimized with early discontinuation gives a hopeful message for patients who struggle with addiction and psychosis,” wrote a global team of researchers, led by a group in Norway. “Addressing substance use as early as possible is critical, as early substance use termination predicts better long-term outcome.”The study was a naturalistic, longitudinal follow-up of a large, clinical epidemiological sample collected consecutively from four Scandinavian health care sectors, with a combined estimated population of 665,000 inhabitants.Inclusion criteria included being 15 to 65 years old; living in one of the participating sites; and having first-episode schizophrenia, schizophreniform disorder or schizoaffective disorder, delusional disorder, mood disorder with mood-incongruent psychotic features, brief psychotic disorder, or psychosis not otherwise specified.Three hundred and one patients were included between 1997 and 2001 and followed up at three months and at 1, 2, 5, and 10 years. Symptom remission was defined as having no score of 4 or higher for the past six months on any of the following items on the Positive and Negative Syndrome Scale (PANSS): delusions, disorganized thought, hallucinatory behavior, affective flattening, passive social withdrawal, lack of spontaneity, bizarre posture, or unusual thought content.Recovery was defined as a combination of symptom remission and adequate social functioning according to the Strauss-Carpenter Level of Functioning score. This includes at least 12 months of work or study full time, living independently, seeing friends at least once a week, and not having been hospitalized.Of the 301 patients, 266 could be classified into one of four groups based on their patterns of substance use in the first two years after diagnosis: persistent users (n=43), episodic users (n=48), stop-users (stopped substance use within two years after diagnosis, n=34), and nonusers (n=141). There were 35 patients about whom substance use data were incomplete and who could not be designated into any of the four categories. After 10 years, stop-users had similar symptom profiles as nonusers, and both groups had fewer symptoms than episodic or persistent users. In fact, while persistent users had PANSS negative scores that increased over the 10-year period, the negative scores of stop-users decreased over time.“Our results, showing improvement in negative symptoms with cessation of substance use are of interest as these are symptoms that are difficult to treat with antipsychotics. In addition, these symptoms are closely linked to daily and social functioning and quality of life,” the authors concluded. ■An abstract of “The Effect of Substance Use on 10-Year Outcome in First-Episode Psychosis” can be accessed here. ISSUES NewArchived

Treatment response in nonpsychotic vs psychotic manias - A follow up study from India.

Studies on treatment outcome in mania had been many. A few studies from the west address the issue of outcome in mood congruent and mood incongruent manias. None could be found from India. To compare the treatment response in three groups of patients with mania- Nonpsychotic, psychotic with mood congruent and psychotic with mood incongruent features. All consecutive manic patients admitted during 2013 to 2014, meeting inclusion and exclusion criteria were taken up. 28 patients with nonpsychotic Mania, 10 with mood congruent psychotic symptoms (MIC-) & 12 with mood incongruent psychotic features (MIC+). Diagnosis was confirmed using SCID. Mood stabilizers and Olanzapine or equivalent doses of antipsychotics were administered. Semi structured proforma was used for Socio Demographic & clinical details. YMRS, HDRS, Semi structured proforma to assess response (ISBD recommendations), CGI -BP & SAPS were used. Last 5 tools to assess the response to treatment at every 2 weeks, for 8 weeks. Statistical Package for Social Sciences, version 17.0 was used. These three groups did not show statistically significant difference in the socio-demographic variables. Severity of Mania was higher in Psychotic Mania. Psychotic Manias (group 2 and 3 combined) showed longer response time. However, mood incongruent psychotic manias when compared against the other 2 groups clubbed together did not differ significantly. All patients were from a tertiary referral centre and were hospitalized. Majority of them had a past history. The sample sizes were small. Treatment could not be fully matched. Our findings support the view that psychotic manias on the whole take significantly longer time than mania without psychotic symptoms to respond, and also scored higher on indices of severity. Mood Incongruent Psychotic Manias and Mood Congruent Psychotic Manias did not differ in severity & response time.

Structural brain changes in first episode mania with and without psychosis: Data from the Systematic Treatment Optimization Program for Early Mania (STOP-EM)

Objectives: The neurobiological underpinnings of bipolar I disorder are not yet understood. Previous structural neuroimaging studies of bipolar disorder have produced rather conflicting results. We hypothesise that clinical sub-phenotypes of bipolar I disorder defined by their psychotic symptoms, especially those with mood-incongruent psychotic features, may have more extensive structural brain abnormalities.Methods: We investigated structural brain alterations in patients with first-episode mania (n = 55) with mood-congruent (n = 16) and mood-incongruent (n = 32) psychotic features, as well as those without psychotic symptoms (n = 7), relative to healthy subjects (n = 56).Results: Total intracranial volume was significantly reduced in patients with mood-incongruent psychosis compared to healthy subjects while cerebrospinal fluid (CSF) volume was significantly increased. Patients with mood-congruent psychosis showed significant reduction in total white matter volume and significant CSF volume increase. Patients with psychosis had significant volume reduction in anterior cingulate and medial prefrontal cortices. Relative to mood-congruent psychotic features, mood-incongruent psychotic features were associated with volume reduction in the left middle temporal gyrus, right inferior parietal gyrus, right fusiform gyrus, left middle orbitofrontal gyrus and cerebellum.Conclusions: While preliminary, our findings suggest that the presence and type of psychosis in first-episode mania may be phenotypic markers of underlying biological variants of bipolar disorder.

Genome-wide association of mood-incongruent psychotic bipolar disorder.

Mood-incongruent psychotic features (MICP) are familial symptoms of bipolar disorder (BP) that also occur in schizophrenia (SZ), and may represent manifestations of shared etiology between the major psychoses. In this study we have analyzed three large samples of BP with imputed genome-wide association data and have performed a meta-analysis of 2196 cases with MICP and 8148 controls. We found several regions with suggestive evidence of association (P<10–6), although no marker met genome-wide significance criteria. The top associations were on chromosomes: 6q14.2 within the PRSS35/SNAP91 gene complex (rs1171113, P=9.67 × 10–8); 3p22.2 downstream of TRANK/LBA1 (rs9834970, P=9.71 × 10–8); and 14q24.2 in an intron of NUMB (rs2333194, P=7.03 × 10–7). These associations were present in all three samples, and both rs1171113 and rs2333194 were found to be overrepresented in an analysis of MICP cases compared with all other BP cases. To test the relationship of MICP with SZ, we performed polygenic analysis using the Psychiatric GWAS Consortium SZ results and found evidence of association between SZ polygenes and the presence of MICP in BP cases (meta-analysis P=0.003). In summary, our analysis of the MICP phenotype in BP has provided suggestive evidence for association of common variants in several genes expressed in the nervous system. The results of our polygenic analysis provides support for a modest degree of genetic overlap between BP with MICP and SZ, highlighting that phenotypic correlations across syndromes may be due to the influence of polygenic risk factors.

Early determinants of four‐year clinical outcomes in bipolar disorder with psychosis

Bipolar disorder with psychosis is common in inpatient settings and is associated with diverse outcomes after hospital discharge, which can range from a return to premorbid functioning with no recurrence, to a chronic or recurring illness. Less is known, however, about factors that can predict a better or worse clinical outcome. The present study sought to assess four-year clinical outcomes and their predictors in patients hospitalized for bipolar I disorder with psychosis. Participants from the Suffolk County Mental Health Project (SCMHP) with a baseline diagnosis of bipolar I disorder with psychotic features (N=126) were reassessed using face-to-face interviews at six months, two years, and four years following their first hospitalization. At each time point, clinical status, role functioning, and treatment were assessed by highly trained interviewers using standardized instruments. The majority of participants (73.2%) returned to their premorbid level of role functioning by the four-year follow-up and the median percentage of time ill during the interval was less than 20%. Nevertheless, almost half of the sample (46.9%) was rehospitalized at least once. Psychotic symptoms at baseline (particularly Schneiderian symptoms), depressive phenomenology, childhood psychopathology, and younger age at first hospitalization predicted worse outcome, whereas mood-incongruent psychotic features and age of mood disorder onset did not. The four-year outcomes of a first-admission cohort with bipolar I disorder with psychosis were generally favorable. Poorer premorbid functioning, Schneiderian delusions, greater depressive symptoms, and a younger age of first hospitalization portend a worse course.

Two-year outcomes in first-episode psychotic depression

Early assessment can guide accurate diagnosis, prognosis, and treatment-planning for patients with major mental illnesses. Longitudinal studies in psychotic depression from onset are rare, encouraging the present study. We followed 56 DSM-IV MDD patients with psychotic features prospectively and systematically to assess course and predictors of operationally-defined syndromal remission, syndromal recovery, symptomatic remission, functional recovery, and new episodes, and to evaluate diagnostic stability. Among 49/56 cases followed for ≥2 years, 59% retained the initial diagnosis and most achieved syndromal remission (86%) and recovery (84%); 58% remitted symptomatically, and only 35% (17/49) recovered functionally. Syndromal recovery was earlier following subacute onset, lower initial depression scores, and lack of moodincongruent psychotic features. Within 2 years, 45% (22/49) experienced new episodes - earlier with younger onset and higher CGI scores. DSM diagnosis changed in 41%, to bipolar (33%), or schizoaffective disorders (12%), which followed early mania-like or schizophrenia-like features, respectively. Within 2 years of first-hospitalizations, 41% of patients initially diagnosed with psychotic-depression met criteria for DSM-IV bipolar or schizoaffective disorders. Of the 59% retaining the initial diagnosis for 2 years, nearly half experienced new episodes, 42% remained symptomatic, and two-thirds failed to regain their own prior functional status.

Exonic DNA Sequencing of ERBB4 in Bipolar Disorder

The Neuregulin-ErbB4 pathway plays a crucial role in brain development and constitutes one of the most biologically plausible signaling pathways implicated in schizophrenia and, to a lesser extent, in bipolar disorder (BP). However, recent genome-wide association analyses have not provided evidence for common variation in NRG1 or ERBB4 influencing schizophrenia or bipolar disorder susceptibility. In this study, we investigate the role of rare coding variants in ERBB4 in BP cases with mood-incongruent psychotic features, a form of BP with arguably the greatest phenotypic overlap with schizophrenia. We performed Sanger sequencing of all 28 exons in ERBB4, as well as part of the promoter and part of the 3′UTR sequence, hypothesizing that rare deleterious variants would be found in 188 cases with mood-incongruent psychosis from the GAIN BP study. We found 42 variants, of which 16 were novel, although none were non-synonymous or clearly deleterious. One of the novel variants, present in 11.2% of cases, is located next to an alternative stop codon, which is associated with a shortened transcript of ERBB4 that is not translated. We genotyped this variant in the GAIN BP case-control samples and found a marginally significant association with mood-incongruent psychotic BP compared with controls (additive model: OR = 1.64, P-value = 0.055; dominant model: OR = 1.73. P-value = 0.039). In conclusion, we found no rare variants of clear deleterious effect, but did uncover a modestly associated novel variant that could affect alternative splicing of ERBB4. However, the modest sample size in this study cannot definitively rule out a role for rare variants in bipolar disorder and studies with larger sample sizes are needed to confirm the observed association.

A 36-Year-Old Man with Agitated Behavior, Psychosis

The patient was a single, 36year-old white man. He was admitted to our institution due to agitated behavior and psychosis, with a diagnosis of bipolar I disorder from his most recent episode, which was mixed and severe with moodincongruent psychotic features. He presented with depressed mood of 3 weeks’ duration, associated with early and intermittent insomnia, decreased energy, racing thoughts, and psychomotor agitation. Furthermore, he exhibited persecutory delusions, believing that people were “out to get him,” and was thus physically aggressive to those he encountered. He denied any suicidal or homicidal ideations, and substance abuse screens returned with negative results. The patient was diagnosed with myasthenia gravis at 19 years, but because he was “living on the streets,” he failed to receive adequate treat-

Mood-incongruent psychosis in bipolar disorder: conditional linkage analysis shows genome-wide suggestive linkage at 1q32.3, 7p13 and 20q13.31.

The majority of research into functional psychosis has proceeded under the assumption that schizophrenia and bipolar disorder are distinct entities with separate underlying disease processes and treatments. This view has been increasingly challenged in both clinical and genetic studies. Findings in recent association studies at two specific genes suggest that the occurrence of mood-incongruent psychotic features may indicate a relatively homogeneous subset of the bipolar phenotype. We examined this hypothesis. Caucasian affected individuals were ascertained from Europe (the United Kingdom, the Republic of Ireland, Germany, Italy and Andalusia). Consensus best-estimate diagnoses were assigned by two independent raters according to all available information. There was no cross-site evaluation of inter-rater reliability. Families multiply affected by bipolar spectrum mood disorder were selected, comprising 383 affected relative pairs. Individuals were considered to be affected if they were diagnosed with DSM-IV bipolar I disorder or schizoaffective disorder, bipolar type. Multipoint, affected relative pair covariate linkage analysis was performed. Significant familiality of incongruent psychosis was observed [intra-class correlation coefficient (ICC) = 0.309; p = 0.001, one-tail]. Covariate linkage analysis provided three regions with genome-wide suggestive evidence for linkage on chromosomes 1q32.3 (LOD = 4.15, expected 0.12 times per genome scan), 7p13 (LOD = 3.32) and 20q13.31 (LOD = 2.98). No region in our analysis met criteria for genome-wide significance. Our results provide molecular support for the hypothesis that genes may exist for specific forms of bipolar illness, dependent on the presence or absence of incongruent psychosis. Our findings suggest that researchers should take account of mood-congruence/incongruence of psychotic features in studies of bipolar disorder.

Family‐based association study of Neuregulin 1 with psychotic bipolar disorder

The Neuregulin 1 gene (NRG1) has been associated with schizophrenia, and, to a lesser extent, with bipolar disorder (BP). We investigated the association of NRG1 with BP in a large family sample, and then performed analyses according to the presence of psychotic features or mood-incongruent psychotic features. We genotyped 116 tagSNPs and four Icelandic "core" SNPs in 1,199 subjects from 314 nuclear families. Of 515 BP offspring, 341 had psychotic features, and 103 had mood-incongruent psychotic features. In single-marker and sliding window haplotype analyses using FBAT, there was little association using the standard BP or mood-incongruent psychotic BP phenotypes, but stronger signals were seen in the psychotic BP phenotype. The most significant associations with psychotic BP were in haplotypes within the 5' "core" region. The strongest global P-value was across three SNPs: NRG241930-NRG243177-rs7819063 (P = 0.0016), with an undertransmitted haplotype showing an individual P = 0.0007. The most significant individual haplotype was an undertransmitted two-allele subset of the above (NRG243177-rs7819063, P = 0.0004). Additional associations with psychotic BP were found across six SNPs in a 270 kb central region of the gene. The most 3' of these, rs7005606 (P = 0.0029), is located approximately 4 kb from the type I NRG1 isoform promoter. In sum, our study suggests that NRG1 may be specifically associated with the psychotic subset of BP; however, our results should be interpreted cautiously since they do not meet correction for multiple testing and await independent replication.

An association study of the neuregulin 1 gene, bipolar affective disorder and psychosis

As evidence of partial aetiological overlap between bipolar affective disorder and schizophrenia is accumulating, it is important to determine whether genes implicated in the aetiology of schizophrenia play a role in bipolar disorder, and vice versa. As the neuregulin 1 (NRG1) gene has been associated with schizophrenia, we set out to investigate whether it is also associated with bipolar affective disorder, using a sample from Scotland, UK. We tested four single nucleotide polymorphisms (SNPs), SNP8NRG221533 (rs35753505), SNP8NRG241930, SNP8NRG243177 (rs6994992) and SNPNRG222662 (rs4623364) for allelic and haplotypic association with bipolar disorder and the presence of psychotic or mood-incongruent psychotic features. We found nominal allele-wise significant association (P = 0.02) for SNP8NRG221533, with the T allele being overrepresented in cases. This is the opposite allelic association to the original association study where the C allele was associated with schizophrenia. Allele-wise significance increased when we tested for association with the subgroups of bipolar disorder with psychotic features (chi2 = 8.53; P = 0.003; odds ratio = 1.49) and, more specifically, with mood-incongruent psychotic features (chi2 = 7.13; P = 0.008; odds ratio = 1.57). Furthermore, both these subphenotypes were significantly associated with the SNP8NRG221533(T)-SNP8NRG241930(G) haplotype (chi2 = 11.94, global P = 0.027 and chi2 = 11.88, global P = 0.019, respectively) and with the SNP8NRG221533(T)-SNP8NRG222662(C)-SNP8NRG241930(G) haplotype (chi2 = 19.98, global P = 0.009) in case of the broader subphenotype of psychotic bipolar. This study supports the hypothesis that NRG1 may play a role in the development of bipolar disorder, especially in psychotic subtypes, albeit with different alleles to previous association reports in schizophrenia and bipolar disorder.

Adjunctive Use of Methylphenidate in the Treatment of Psychotic Unipolar Depression

Adjunctive use of methylphenidate, a central stimulant, has been considered as a potential therapeutic choice for patients with refractory unipolar depression, geriatric depression, bipolar depression, and depression secondary to a medical illness. We present a case of psychotic unipolar depression in which the patient responded significantly to the adjunctive use of methylphenidate. A 45-year-old woman had melancholic depressive symptoms and mood incongruent psychotic features during her second episode of unipolar depression. She attempted suicide by hanging herself and was forcibly hospitalized. She was initially treated with venlafaxine (262.5 mg/d), olanzapine (20 mg/d), and benzodiazepines. However, she responded unsatisfactorily to the combination treatment. Because her family refused electroconvulsive treatment, we added methylphenidate to her medications for adjunctive use. The dose of methylphenidate was started at a dose of 5 mg/d. It was not until the patient received 30 mg/d of methylphenidate that her persistent psychosis and severe depression were substantially improved. She tolerated her medications well and did not report any side effects. She was discharged in a stable condition 2 weeks after the adjunctive use of methylphenidate. The patient's methylphenidate was gradually tapered and finally discontinued. To date, she remains well and is regularly followed up at our outpatient clinic. Our case suggests that adjunctive use of methylphenidate can be a therapeutic option in treating some patients with psychotic unipolar depression who do not adequately respond to the combination treatment of an antidepressant and an atypical antipsychotic. Further controlled studies are warranted to verify this.

Mood-Incongruent Psychotic Features in Bipolar Disorder: Familial Aggregation and Suggestive Linkage to 2p11-q14 and 13q21-33

Mood-incongruent psychotic features in bipolar disorder may signify a more severe form of the illness and might represent phenotypic manifestations of susceptibility genes shared with schizophrenia. This study attempts to characterize clinical correlates, familial aggregation, and genetic linkage in subjects with these features. Subjects were drawn from The National Institute of Mental Health (NIMH) Genetics Initiative Bipolar Disorder Collaborative cohort, consisting of 708 families recruited at 10 academic medical centers. Subjects with mood-incongruent and mood-congruent psychotic features were compared on clinical variables. Familial aggregation was tested using a proband-predictive model and generalized estimating equations. A genome-wide linkage scan incorporating a mood-incongruence covariate was performed. Mood-incongruent psychotic features were associated with an increased rate of hospitalization and attempted suicide. A proband with mood-incongruence predicted mood-incongruence in relatives with bipolar I disorder when compared with all other subjects and when compared with subjects with mood-congruent psychosis. The presence of mood-incongruent psychotic features increased evidence for linkage on chromosomes 13q21-33 and 2p11-q14. These logarithm of the odds ratio (LOD) scores and their increase from baseline met empirical genome-wide suggestive criteria for significance. Mood-incongruent psychotic features showed evidence of a more severe course, familial aggregation, and suggestive linkage to two chromosomal regions previously implicated in major mental illness susceptibility. The 13q21-33 finding supports prior evidence of bipolar disorder/schizophrenia overlap in this region, while the 2p11-q14 finding is, to the authors' knowledge, the first to suggest that this schizophrenia linkage region might also harbor a bipolar disorder susceptibility gene.

Mood-Incongruent Psychotic Features in Bipolar Disorder: Familial Aggregation and Suggestive Linkage to 2p11-q14 and 13q21-33

Objective: Mood-incongruent psychotic features in bipolar disorder may signify a more severe form of the illness and might represent phenotypic manifestations of susceptibility genes shared with schizophrenia. This study attempts to characterize clinical correlates, familial aggregation, and genetic linkage in subjects with these features. Method: Subjects were drawn from The National Institute of Mental Health (NIMH) Genetics Initiative Bipolar Disorder Collaborative cohort, consisting of 708 families recruited at 10 academic medical centers. Subjects with mood-incongruent and mood-congruent psychotic features were compared on clinical variables. Familial aggregation was tested using a proband-predictive model and generalized estimating equations. A genome-wide linkage scan incorporating a mood-incongruence covariate was performed. Results: Mood-incongruent psychotic features were associated with an increased rate of hospitalization and attempted suicide. A proband with mood-incongruence predicted mood-incongruence in relatives with bipolar I disorder when compared with all other subjects and when compared with subjects with mood-congruent psychosis. The presence of mood-incongruent psychotic features increased evidence for linkage on chromosomes 13q21-33 and 2p11-q14. These logarithm of the odds ratio (LOD) scores and their increase from baseline met empirical genome-wide suggestive criteria for significance. Conclusions: Mood-incongruent psychotic features showed evidence of a more severe course, familial aggregation, and suggestive linkage to two chromosomal regions previously implicated in major mental illness susceptibility. The 13q21-33 finding supports prior evidence of bipolar disorder/schizophrenia overlap in this region, while the 2p11-q14 finding is, to the authors’ knowledge, the first to suggest that this schizophrenia linkage region might also harbor a bipolar disorder susceptibility gene.

Size Matters: The Unexpected Challenge of Detecting Linkage in Large Cohorts

Size Matters: The Unexpected Challenge of Detecting Linkage in Large Cohorts