Infection, treatment and immune response in patients with bipolar disorder versus patients with major depression, schizophrenia or healthy controls

Hinze-Selch D. Infection, treatment and immune response in patients with bipolar disorder versus patients with major depression, schizophrenia or healthy controls. Bipolar Disord 2002: 4(Suppl. 1): 81–83. ©Blackwell Munksgaard, 2002
Bipolar disorder is the least studied among the three major psychiatric disorders of schizophrenia, major depression and bipolar disorder. Furthermore, investigations on infection and immunity in bipolar disorder make up only a small portion of the sparse research done on this disorder. However, there are reports that modulation of the immune system and certain infections might be associated with bipolar disorder and that there might be differences between bipolar and the other disorders. The purpose of this paper is to briefly review published data on these issues in bipolar versus the other disorders, and to present an ongoing clinical study on the putative involvement of infection with the parasite Toxoplasma gondii in these three major psychiatric disorders.     

Tobacco smoking behaviors in bipolar disorder: a comparison of the general population,schizophrenia, and major depression

Objectives: This study compared the prevalence of tobacco smoking behaviors in patients with bipolar disorder with normal and psychiatric (schizophrenia and major depression) controls. The main goal was to establish that bipolar patients smoke more than normal controls. Differences with psychiatric controls were explored. Methods: Samples of 424 patients (99 bipolar, 258 schizophrenia and 67 major depression) and 402 volunteer controls were collected in Central Kentucky. Smoking data for Kentucky’s general population were available. Odds ratios (ORs) and their 95% confidence intervals (CIs) were used to establish the strength of associations. Logistic regression was used to adjust ORs for confounding variables. Results: Using epidemiological definitions of smoking behaviors and the general population as controls provided bipolar disorder unadjusted ORs of 5.0 (95% CI: 3.3–7.8) for current cigarette smoking, 2.6 (95% CI: 1.7–4.4) for ever cigarette smoking, and 0.13 (95% CI: 0.03–0.24) for smoking cessation. Using a clinical definition and volunteers as controls provided respective bipolar disorder adjusted ORs of 7.3 (95% CI: 4.3–12.4), 4.0 (95% CI: 2.4–6.7), and 0.15 (95% CI: 0.06–0.36). Prevalences of current daily smoking for patients with major depression, bipolar disorder, and schizophrenia were 57%, 66%, and 74%, respectively. Conclusions: Bipolar disorder was associated with significantly higher prevalences of tobacco smoking behaviors compared with the general population or volunteer controls, independently of the definition used. It is possible that smoking behaviors in bipolar disorder may have intermediate prevalences between major depression and schizophrenia, but larger samples or a combination of multiple studies (meta‐analysis) will be needed to establish whether this hypothesis is correct.     

Clinical predictors of acute response with quetiapine in psychotic mood disorders

BACKGROUND: In controlled studies of patients with schizophrenia, the atypical antipsychotic quetiapine, 300 mg/day, has been shown to be as effective in the treatment of positive and negative symptoms as haloperidol. However, little is known about the efficacy of quetiapine in patients with psychotic mood disorders. The purpose of this study was to assess the efficacy of quetiapine in the treatment of psychotic mood disorders in comparison with nonaffective psychotic disorders and identify clinical factors associated with quetiapine response. METHOD: In a naturalistic setting, by reviewing medical records, we assessed response to quetiapine and factors associated with response to quetiapine in 145 consecutive patients newly treated with the drug at a nonprofit academic psychiatric hospital. These patients had received a discharge diagnosis of bipolar disorder (manic, mixed, or depressive type), major depression with psychotic features, schizophrenia, schizoaffective disorder (bipolar or depressive type), delusional disorder, or psychosis not otherwise specified (NOS) according to DSM-IV criteria. RESULTS: Patients with a diagnosis of bipolar disorder, manic, mixed, or depressed and schizoaffective disorder, bipolar type displayed higher response rates (> 74%) compared with patients with schizophrenia. However, this finding did not achieve statistical significance. A diagnosis of major depression with psychotic features (p = .02) and longer duration of illness (p = .03) were associated with less chance of responding. CONCLUSION: Quetiapine may be a useful alternative or adjunctive treatment for patients with bipolar and schizoaffective disorders.     

Reduction in Reelin immunoreactivity in hippocampus of subjects with schizophrenia, bipolar disorder and major depression

Accumulation of neurobiological knowledge points to neurodevelopmental origins for certain psychotic and mood disorders. Recent landmark postmortem reports implicate Reelin, a secretory glycoprotein responsible for normal lamination of brain, in the pathology of schizophrenia and bipolar disorders. We employed quantitative immunocytochemistry to measure levels of Reelin protein in various compartments of hippocampal formation in subjects diagnosed with schizophrenia, bipolar disorder and major depression compared to normal controls. Significant reductions were observed in Reelin-positive adjusted cell densities in the dentate molecular layer (ANOVA, P < 0.001), CA4 area (ANOVA, P < 0.001), total hippocampal area (ANOVA, P < 0.038) and in Reelin-positive cell counts in CA4 (ANOVA, P < 0.042) of schizophrenics vs controls. Adjusted Reelin-positive cell densities were also reduced in CA4 areas of subjects with bipolar disorder (ANOVA, P < 0.001) and nonsignificantly in those with major depression. CA4 areas were also significantly reduced in schizophrenic (ANOVA, P < 0.009) patients. No significant effects of confounding variables were found. The exception was that family history of psychiatric illness correlated strongly with Reelin reductions in several areas of hippocampus (CA4, adjusted cell density, F = 13.77, P = 0.001). We present new immunocytochemical evidence showing reductions in Reelin expression in hippocampus of subjects with schizophrenia, bipolar disorder and major depression and confirm recent reports documenting a similar deficit involving Reelin expression in brains of subjects with schizophrenia and bipolar disorder.     

Sustained unemployment in psychiatric outpatients with bipolar depression compared to major depressive disorder with comorbid borderline personality disorder

Zimmerman M, Martinez JH, Young D, Chelminski I, Dalrymple K. Sustained unemployment in psychiatric outpatients with bipolar depression compared to major depressive disorder with comorbid borderline personality disorder. Bipolar Disord 2012: 14: 856–862. © 2012 John Wiley & Sons A/S.Published by Blackwell Publishing Ltd. Objectives: The morbidity associated with bipolar disorder is, in part, responsible for repeated calls for improved detection and recognition. No such clinical commentary exists for improved detection of borderline personality disorder in depressed patients. Clinical experience suggests that borderline personality disorder is as disabling as bipolar disorder; however, no studies have directly compared the two disorders. For this reason we undertook the current analysis from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project comparing unemployment and disability rates in patients with bipolar disorder and borderline personality disorder. Methods: Patients were interviewed with semi‐structured interviews. We compared three non‐overlapping groups of depressed patients: (i) 181 patients with DSM–IV major depressive disorder and borderline personality disorder, (ii) 1068 patients with major depressive disorder without borderline personality disorder, and (iii) 84 patients with bipolar depression without borderline personality disorder. Results: Compared to depressed patients without borderline personality disorder, depressed patients with borderline personality disorder were significantly more likely to have been persistently unemployed. A similar difference was found between patients with bipolar depression and major depressive disorder without borderline personality disorder. No differences were found between patients with bipolar depression and depression with borderline personality disorder. Conclusions: Both bipolar disorder and borderline personality disorder were associated with impaired occupational functioning and thus carry a significant public health burden. Efforts to improve detection of borderline personality disorder in depressed patients might be as important as the recognition of bipolar disorder.     

COMT genetic variation confers risk for psychotic and affective disorders: a case control study

Background  

Variation in the COMT gene has been implicated in a number of psychiatric disorders, including psychotic, affective and anxiety disorders. The majority of these studies have focused on the functional Val108/158Met polymorphism and yielded conflicting results, with limited studies examining the relationship between other polymorphisms, or haplotypes, and psychiatric illness. We hypothesized that COMT variation may confer a general risk for psychiatric disorders and have genotyped four COMT variants (Val158Met, rs737865, rs165599, and a SNP in the P2 promoter [-278A/G; rs2097603]) in 394 Caucasian cases and 467 controls. Cases included patients with schizophrenia (n = 196), schizoaffective disorder (n = 62), bipolar disorder (n = 82), major depression (n = 30), and patients diagnosed with either psychotic disorder NOS or depressive disorder NOS (n = 24).     

Psychopathology in the offspring of parents with bipolar disorder: a controlled study.

BACKGROUND: To examine the risk for psychopathology in offspring at risk for bipolar disorder and the course of psychiatric disorders in these youth. METHODS: Using structured diagnostic interviews (Structured Clinical Interview for DSM-IV [SCID] and Kiddie Schedule for Affective Disorders and Schizophrenia [K-SADS]), psychiatric diagnoses of 117 nonreferred offspring of parents with diagnosed bipolar disorder were compared with those of 171 age- and gender-matched offspring of parents without bipolar disorder or major depression. RESULTS: Compared with offspring of parents without mood disorders, high-risk youth had elevated rates of major depression and bipolar disorder, anxiety, and disruptive behavior disorders. High-risk offspring also had significantly more impaired Global Assessment of Functioning (GAF) scores, higher rates of psychiatric treatment, and higher rates of placement in special education classes. Disruptive behavior disorders, separation anxiety disorder, generalized anxiety disorder (GAD), social phobia, and depression tended to have their onset in early or middle childhood, whereas bipolar disorder, obsessive-compulsive disorder (OCD), panic disorder, and substance use disorder had onset most frequently in adolescence. CONCLUSIONS: These findings support the hypothesis that offspring of parents with bipolar disorder are at significantly increased risk for developing a wide range of severe psychiatric disorders and accompanying dysfunction. Early disruptive behavior and anxiety disorders, as well as early-onset depression, may be useful markers of risk for subsequent bipolar disorder in high-risk samples.     

Suicide attempts and clinical risk factors in patients with bipolar and unipolar affective disorders

Background

Suicide is an important clinical problem in psychiatric patients. The highest risk of suicide attempts is noted in affective disorders.

Objective

The aim of the study was to look for suicide risk factors among sociodemographic and clinical factors, family history and stressful life events in patients with diagnosis of unipolar and bipolar affective disorder (597 patients, 563 controls).

Method

In the study, the Structured Clinical Interview for DSM-IV Axis I Disorders and the Operational Criteria Diagnostic Checklist questionnaires, a questionnaire of family history, and a questionnaire of personality disorders and life events were used.

Results

In the bipolar and unipolar affective disorders sample, we observed an association between suicidal attempts and the following: family history of psychiatric disorders, affective disorders and psychoactive substance abuse/dependence; inappropriate guilt in depression; chronic insomnia and early onset of unipolar disorder. The risk of suicide attempt differs in separate age brackets (it is greater in patients under 45 years old). No difference in family history of suicide and suicide attempts; marital status; offspring; living with family; psychotic symptoms and irritability; and coexistence of personality disorder, anxiety disorder or substance abuse/dependence with affective disorder was observed in the groups of patients with and without suicide attempt in lifetime history.     

Is death from natural causes still excessive in psychiatric patients? A follow-up of 1593 patients with major affective disorder

A follow-up of 1593 Iowans with major affective disorder showed excessive mortality from unnatural causes in primary and secondary depression, and bipolar depression, but not mania, compared with age- and sex-matched controls from the general population. Excessive death from natural causes was found in women with secondary unipolar depression and bipolar depression and in manics (men and women combined) who had concurrent organic mental disorders or serious medical illnesses. Natural death was not excessive in the absence of these conditions. We conclude that excessive natural death reported in psychiatric patients is due to complicating physical disorders and not to the primary psychiatric disorder per se, whereas excessive unnatural death is due to the psychiatric disorder. Also, psychiatrically ill persons are probably referred for hospitalization more frequently when complicating physical disorders are present. Finally, we conclude that mortality patterns were similar in patients with primary and secondary unipolar depression, but bipolar patients were at lower risk for unnatural death than were unipolar patients.     

Deficits in GABA(B) receptor system in schizophrenia and mood disorders: a postmortem study

Postmortem and genetic studies have clearly demonstrated changes in GABA(B) receptors in neuropsychiatric disorders such as autism, bipolar disorder, major depression, and schizophrenia. Moreover, a number of recent studies have stressed the importance of cerebellar dysfunction in these same disorders. In the current study, we examined protein levels of the two GABA(B) receptor subunits GABBR1 and GABBR2 in lateral cerebella from a well-characterized cohort of subjects with schizophrenia (n=15), bipolar disorder (n=14), major depression (n=13) and healthy controls (n=12). We found significant reductions in protein for both GABBR1 and GABBR2 in lateral cerebella from subjects with schizophrenia, bipolar disorder and major depression when compared with controls. These results provide further evidence of GABAergic dysfunction in these three disorders as well as identify potential targets for therapeutic intervention.     

Differential diagnosis between dissociative disorders and schizophrenia

The differential diagnosis of dissociative disorders includes many psychiatric disorders, such as schizophrenia, bipolar disorders (especially bipolar II disorder), depressive disorder (especially atypical depression), epilepsy, Asperger syndrome, and borderline personality disorder. The theme of this paper is the differential diagnosis between dissociative disorders and schizophrenia. Schneiderian first-rank symptoms in schizophrenia are common in dissociative disorders, especially in dissociative identity disorder (DID). Many DID patients have been misdiagnosed as schizophrenics and treated with neuroleptics. We compared and examined Schneiderian symptoms of schizophrenia and those of dissociative disorders from a structural viewpoint. In dissociative disorders, delusional perception and somatic passivity are not seen. "Lateness" and "Precedence of the Other" originated from the concept of "Pattern Reversal" (H. Yasunaga)" is characteristic of schizophrenia. It is important to check these basic structure of schizophrenia in subjective experiences in differential diagnosis between dissociative disorders and schizophrenia.     

Dimensions underlying psychotic and manic symptomatology: Extending normal-range personality traits to schizophrenia and bipolar spectra

Objective

Covariance among psychiatric disorders can be accounted for by higher-order internalizing, externalizing, and psychosis dimensions, but placement of bipolar disorder within this framework has been inconsistent. Moreover, whether deviations in normal-range personality can explain psychosis and vulnerability to severe mood lability, as seen in schizophrenia and bipolar disorder, remains unclear.

Methods

Exploratory factor analysis of interviewer-rated clinical symptoms in patients with schizophrenia or bipolar disorder, their first-degree biological relatives, and nonpsychiatric controls (total N = 193), followed by examination of associations between symptom dimensions and self reports on personality questionnaires.

Results

Covariance in symptoms was accounted for by five factors: positive symptoms of psychosis, negative symptoms of psychosis, disorganization, mania, and depression/anxiety. Schizophrenia and bipolar patients/relatives reported elevated negative emotionality and absorption and lower positive emotionality relative to controls. Personality did not differ between schizophrenia and bipolar patients/relatives, but there was a different pattern of associations between symptoms and personality in these groups.

Conclusions

Discrete dimensions reflecting psychotic, manic, and depressive symptoms emerge when a broad set of clinical symptoms is examined in a sample overrepresented by psychotic experiences and affective disturbances. Although normal-range personality traits index common phenotypes spanning schizophrenia and bipolar spectra, the same symptoms may carry different significance across disorders.     

Reading problems and major mental disorders - co-occurrences and familial overlaps in a Swedish nationwide cohort

Reading problems often co-occur with ADHD and conduct disorder. However, the patterns of co-occurrence and familial overlap between reading problems and other psychiatric disorders have not been systematically explored. We conducted a register-based cohort study including 8719 individuals with reading problems and their siblings, along with matched comparison individuals. Conditional logistic regressions estimated risks for ADHD, autism, obsessive-compulsive disorder, anorexia nervosa, schizophrenia, bipolar disorder, depression, substance use disorder, and violent/non-violent criminality in individuals with reading problems and their siblings. Diagnoses of psychiatric disorders were physician-assigned and ascertained from the Swedish National Patient Register, and crime convictions from the Swedish National Crime Register. We found that individuals with reading problems had excess risks for all psychiatric disorders (except anorexia nervosa) and criminality, with risk ratios between 1.34 and 4.91. Siblings of individuals with reading problems showed excess risks for ADHD, autism, schizophrenia, bipolar disorder, depression, substance use disorder, and non-violent criminality, with risk ratios between 1.14 and 1.70. In summary, individuals with reading problems had increased risks of virtually all psychiatric disorders, and criminality. The origin of most of these overlaps was familial, in that siblings of individuals with reading problems also had elevated risks of ADHD, autism, schizophrenia, bipolar disorder, depression, substance use disorder, and non-violent criminality. These findings have implications for gene-searching efforts, and suggest that health care practitioners should be alert for signs of psychiatric disorders in families where reading problems exist.     

Lifetime psychopathology in child and adolescent offspring of parents diagnosed with schizophrenia or bipolar disorder: a 2-year follow-up study

Having one parent diagnosed with a severe mental disorder is considered one of the main risk factors for developing that disorder in adulthood, and it also increases the risk of a wide range of mental disorders in the offspring. The aim of this study is to compare the prevalence of several psychopathological diagnoses, the presence of prodromal symptoms, and global functioning in offspring of parents with schizophrenia or bipolar disorder and in offspring of controls at baseline and 2-year follow-up. This study included 41 offspring of parents with schizophrenia, 90 offspring of parents with bipolar disorder, and 107 offspring of controls (mean age 11.7 ± 3.2 at baseline and 13.9 ± 3.2 at follow-up). The prevalence of psychopathology and comorbidity was higher in offspring of parents with schizophrenia and offspring of parents with bipolar disorder than in offspring of controls at baseline and at 2-year follow-up. Interestingly, mood disorders were more prevalent in offspring of parents with bipolar disorder and disruptive disorders were more prevalent in offspring of parents with schizophrenia. Prodromal symptoms were more frequent in offspring of parents with schizophrenia than in offspring of controls, while the offspring of parents with bipolar disorder showed an intermediate pattern. Finally, global functioning was lower in the offspring of parents with schizophrenia than the offspring of parents with bipolar disorder and the offspring of controls. Screening patients’ children is clinically relevant, since, as a group, they have an elevated risk of developing a psychiatric disorder and of experiencing their first symptoms during childhood and adolescence.

     

The plasma levels of interleukin-12 in schizophrenia,major depression,and bipolar mania: effects of psychotropic drugs

Interleukin-12 (IL-12) plays a key role in promoting T helper 1 (Th1) responses and subsequent cell-mediated immunity. Given the role of cytokines in the pathogenesis of psychiatric disorders, the dysregulation of IL-12 in these illnesses would be expected. We measured the plasma levels of IL-12 in 102 psychiatric patients (43 schizophrenia, 34 major depression and 25 bipolar disorder) and 85 normal controls. In addition, IL-12 levels of the patients were measured after an 8-week treatment to assess whether the levels were affected by medication. The IL-12 levels of the patient group with major depression were significantly higher than that of the control group, whereas no differences were found among the other groups. IL-12 values of the three patient groups decreased significantly after 8 weeks of treatment. These findings support the hypothesis that activation of the inflammatory response system and in particular of Th-1-like cells, is involved in the pathophysiology of major depression and that repeated administration of antidepressive and antipsychotic drugs may suppress IL-12 plasma concentrations in psychiatric patients.     

Comorbid Personality Disorders and Violent Behavior in Psychotic Patients

Schizophrenia without any comorbidity confers a modest, but statistically significant elevation of the risk for violence. That risk is considerably increased by comorbid antisocial personality disorder or psychopathy as well as by comorbid substance use disorders. These comorbidities are frequent. Conduct disorder and conduct disorder symptoms elevate the risk for aggressive behavior in patients with schizophrenia. Violence among adults with schizophrenia may follow at least two distinct pathways-one associated with premorbid conditions, including antisocial conduct, and another associated with the acute psychopathology of schizophrenia. Aggressive behavior in bipolar disorder occurs mainly during manic episodes, but it remains elevated in euthymic patients in comparison with controls. The risk of violent behavior is increased by comorbidity with borderline personality disorder, antisocial personality disorder, and substance use disorders. These comorbidities are frequent. Borderline personality disorder and bipolar disorder are related in their phenomenology and response to medication. These two disorders share a tendency to impulsiveness, and impulsive behavior, including impulsive aggression, is particularly expressed when they co-occur.     

Do endogenous features in depression predict the risk of psychiatric illness in relatives?

We sought to evaluate the hypothesis that endogenous symptoms define a form of depression that is relatively distinct from a familial perspective. Cox models examined the relationship between endogenous symptoms in 88 epidemiologically ascertained cases of treated major depression and the risk for a range of psychiatric disorders in relatives. Endogenicity did not predict risk of major depression, bipolar disorder, anxiety disorders, schizophrenia, or schizophrenia spectrum illnesses in relatives. Risk in relatives of illness as an external validator of endogenous depression is not supported by our family study data.     

Dysregulation of glutamate carboxypeptidase II in psychiatric disease

Experimental evidence is beginning to converge on an important role for dysregulation of glutamate carboxypeptidase II (GCPII) in schizophrenia. The goal of this study was to determine GCPII levels in postmortem brain specimens of patients with schizophrenia, bipolar disorder or unipolar depression and age-matched control subjects. We used N-[N-(S)-1,3-dicarboxypropyl]carbamoyl]-S-3-[(125)I]iodo-l-tyrosine ([(125)I]DCIT), a high-affinity radioligand for GCPII, to probe for GCPII expression in prefrontal cortex (PFC) and mesial temporal lobe, two brain regions implicated in the pathophysiology of schizophrenia. We found that GCPII levels measured by [(125)I]DCIT quantitative autoradiography were significantly lower in the PFC and entorhinal cortex in patients with schizophrenia compared to age-matched controls. Patients with bipolar disorder also expressed significantly lower GCPII levels in PFC than controls. The decrease in [(125)I]DCIT binding in schizophrenia and bipolar disorder remained significant after adjusting for drug abuse. A significant difference in GCPII levels was also observed between schizophrenia relative to bipolar disorder and depressed subjects in the hippocampus-stratum lucidum and between schizophrenia and bipolar in the CA2 region of the hippocampus, with bipolar and depressed subjects expressing higher levels of GCPII than subjects with schizophrenia. These differences in hippocampal GCPII levels may implicate differences in the etiologies of these mental disorders. In summary, this study demonstrates a regional dysregulation of GCPII expression in the brain of patients with schizophrenia and other psychiatric disorders and supports a hypoglutamatergic state of the former illness. GCPII may represent a viable therapeutic target for intervention in psychiatric disease.     

Screening psychiatric emergency department patients with major mental illnesses for at-risk drinking

OBJECTIVE: This study determined the prevalence of at-risk drinking in a psychiatric emergency service and compared the characteristics and functioning of at-risk drinkers with schizophrenia or bipolar disorder with those of at-risk drinkers with depression or anxiety disorders. METHODS: Adult patients who entered the psychiatric emergency service and met study criteria were surveyed. RESULTS: A total of 148 participants had schizophrenia or bipolar disorder, and 242 had depression or anxiety. Twenty-three percent of the group with schizophrenia or bipolar disorder and 22 percent of the group with depression or anxiety drank more than the recommended limits. The group with schizophrenia or bipolar disorder reported experiencing significantly more consequences from drinking than the depression or anxiety group. Both groups reported significant depression in the prior few days. CONCLUSIONS: This study demonstrated the importance of assessing alcohol use and depression among all patients in psychiatric emergency services.     

Lifetime rhythmicity and mania as correlates of suicidal ideation and attempts in mood disorders

BACKGROUND: The aim of this study is to establish to what degree variation in lifetime experience of rhythmicity and manic-hypomanic features correlates with suicidality in individuals with mood disorders and other major psychiatric diagnoses and in a comparison group of controls. METHOD: Suicidal ideation and attempts were investigated in a clinical sample, including 77 patients with schizophrenia, 60 with borderline personality disorder, 61 with bipolar disorder, 88 with unipolar depression, and 57 with panic disorder, and in a comparison group of 102 controls. Using information derived from the diagnostic interview and a self-report assessment of mood spectrum symptoms, subjects were assigned to 3 categories according to the maximum level of suicidality achieved in the lifetime (none, ideation/plans, and suicide attempts). The association of categorical and continuous variables with suicidality levels was investigated using multinomial logistic regression models. RESULTS: Suicidal ideation and plans were more common in unipolar depression (50%) and bipolar disorder (42.4%) than in borderline personality disorder (30%), whereas the reverse was true for suicidal attempts. In each of the study groups, the number and the type of mood spectrum items endorsed, including depressive and manic-hypomanic items and rhythmicity and vegetative symptoms, were associated with increased levels of suicidality. CONCLUSIONS: Our results suggest that the assessment of lifetime rhythmicity and manic-hypomanic features may be clinically useful to identify potential suicide attempters in high-risk groups.