Is there a familial overlap between schizophrenia and bipolar disorder?

BACKGROUND: Most investigators accept that schizophrenia and bipolar disorders are distinct entities. The proponents of continuum model have challenged this dichotomy model. METHODS: Information about the first-degree relatives of probands with DSM-IV diagnosis of schizophrenia (n=90), bipolar disorder (n=90), and epilepsy (n=60) was collected by using the Family Interview for Genetic Studies (FIGS). A trained psychiatrist blind to the status of index probands obtained the information. Morbid risk in relatives was calculated using abridged Weinberg's method of age correction. RESULTS: Rates of schizophrenia and bipolar disorder were elevated in the relatives of schizophrenia and bipolar probands, but there was no evidence of coaggregation. The risk for major depression was significantly elevated in the relatives of schizophrenia probands and was comparable to the risk in the relatives of bipolar probands. LIMITATIONS: Family history method was used to obtain information about relatives. Schizoaffective disorder patients were not included in the study and this may have amplified the distinction between schizophrenia and bipolar disorder. CONCLUSIONS: The findings suggest that schizophrenia and bipolar disorders are familially independent, but there could be a familial relationship between the predisposition to schizophrenia and to major depression.     

Is there a relationship between attention deficit hyperactivity disorder and bipolar disorder?

With the increasing recognition of attention deficit hyperactivity disorder (ADHD) in adults and psychotic disorders in children and adolescents, the possibility of a relationship between bipolar disorder (BP) and ADHD has attracted growing interest. This paper critically reviews the scientific literature concerning this postulated relationship by examining evidence from clinico-epidemiological, follow up, family and laboratory studies, including neuroimaging, neuropsychology and genetic studies. The evidence suggests that although the diagnostic categories of BP and ADHD appear to be unrelated, there is support for a possible relationship between some ADHD and manic-like symptoms. However, several fundamental methodological issues require rectification in future research in order to further elucidate the relationship between these disorders.     

Major depressive disorder with anger: a bipolar spectrum disorder?

BACKGROUND: Depression with anger may be more common in bipolar disorders. The aim of the study was to assess whether major depressive disorder (MDD) with anger could be included in the bipolar spectrum, by comparing it to MDD without anger and to bipolar II disorder. METHODS: Consecutive outpatients (281 bipolar II disorder and 202 MDD) presenting for major depressive episode (MDE) treatment were interviewed with the DSM-IV structured clinical interview. Clinical variables used to support the inclusion of MDD with anger in the bipolar spectrum were age of onset, many MDE recurrences, atypical features of depression, depressive mixed state (an MDE plus some concurrent hypomanic symptoms), and bipolar family history. RESULTS: Frequency of MDE with anger was 50.5% [61.2% in bipolar II, and 35.6% in MDD (z = 5.5, p = 0.0000, 95% CI 16.8-43.3%)]. Logistic regression of MDE with anger (dependent variable) versus bipolar variables showed that MDE with anger was significantly associated with all bipolar variables, apart from recurrences. MDD with anger, compared with MDD without anger, had significantly lower age of onset, more marked depressive mixed state, a bipolar family history with more cases, but comparable atypical features and Global Assessment of Functioning scores. MDD with anger, compared with bipolar II disorder, had significantly higher age of onset, less atypical features, and a bipolar family history with less cases. CONCLUSIONS: MDE with anger was common in outpatients (more in bipolar II disorder). MDD with anger may be midway between MDD without anger and bipolar II disorder, and might be included into the bipolar spectrum. However, MDD with anger does not appear to be associated with the often reported negative response to monotherapy with antidepressants.     

Is there a continuity between bipolar and depressive disorders?

BACKGROUND: Recent studies questioned the current categorical split of mood disorders into bipolar disorders (BP) and depressive disorders (MDD). METHODS: Medline database search of papers from the last 10 years on the categorical-dimensional classification of mood disorders. Various combinations of the following key words were used: mood disorders, bipolar, unipolar, major depressive disorder, spectrum, category/categorical, classification, continuity. Only English language clinical papers were included, review papers were excluded, similar papers selected by quality. The number of papers found was 1,141. The number of papers selected was 109. RESULTS: The continuity/spectrum between BP (mainly BP-II) and MDD was supported by the following findings:(1) high frequency of mixed states (mixed mania, mixed hypomania, mixed depression, i.e. co-occurring depression and noneuphoric manic/hypomanic symptoms) because opposite polarity symptoms in the same episode do not support a hypomania/mania-depression splitting; (2) MDD was the most common mood disorder in BP probands' relatives; (3) no bimodal distribution of distinguishing symptoms between BP and MDD; (4) bipolar signs not uncommon in MDD; (5) many MDD shifting to BP; (6) many lifetime manic/hypomanic symptoms in MDD; (7) correlation between lifetime manic/hypomanic symptoms and MDD symptoms; (8) hypomania factors in MDD; (9) MDD often recurrent; (10) similar cognitive style.The categorical distinction between BP (mainly BP-I) and MDD was supported by the following findings: (1) BP more common in BP probands' relatives; (2) lower age at BP onset; (3) females as common as males in BP-I, more common than males in MDD; (4) BP-I depression more atypical and retarded, MDD depression more sleepless and agitated; (5) BP more recurrent. CONCLUSIONS: Focusing on mood spectrum's extremes (BP-I vs. MDD), a categorical distinction seems supported. Focusing on midway disorders (BP-II and MDD plus bipolar signs), a continuity/spectrum seems supported. Results seem to support both a categorical and a dimensional view of mood disorders.     

Is processing speed a valid cognitive endophenotype for bipolar disorder?

ObjectivesThe current study investigated whether a single brief cognitive assessment, processing speed, could be considered as a valid endophenotype for bipolar disorder (BD).MethodsProcessing speed was assessed using the Digit Symbol Test (DST) in 53 euthymic BD probands (BD-P), 50 unaffected first-degree relatives (UFDR) and 60 unrelated healthy controls (HC).ResultsEuthymic BD-P and the UFDR were significantly more impaired on DST performance even after controlling for demography and current mood symptoms (effect sizes 0.89 and 0.52). Clinically significant performance impairment was present in about 30% BD-P and 25% UFDR.LimitationsPharmacotherapy was not controlled for.ConclusionsProcessing speed, as measured with the DST, is a brief reliable measure that could be used in clinical assessments of at risk populations. Our findings support the hypothesis that processing speed may be a valid endophenotype, highly specific for differentiating both euthymic BD-P and UFDR, from HC.     

Is there a specific polysomnographic sleep pattern in children with attention deficit/hyperactivity disorder?

The aim of the study was to characterize the sleep pattern in children with attention deficit/hyperactivity disorder (ADHD). By means of polysomnography (PSG), sleep patterns were studied in 17 unmedicated preadolescent boys rigorously diagnosed with ADHD and 17 control boys precisely matched for age and intelligence. Although ADHD children did not display a general sleep alteration, major PSG data showed a significant increase in the duration of the absolute rapid eye movement (REM) sleep and the number of sleep cycles in ADHD group when compared with controls. In addition, REM sleep latency tended to be shorter in ADHD children. These results suggest that in ADHD children, a forced REM sleep initiation may produce a higher incidence of sleep cycles and may also contribute to an increased duration of the absolute REM sleep. The overall pattern of the findings implies that a forced ultradian cycling appears characteristic for the sleep in ADHD children, which may be related to alterations of brain monoamines and cortical inhibitory control accompanying the ADHD psychopathology.     

Anticipation in bipolar affective disorder: Is age at onset a valid criterion?

Anticipation has been suggested among the genetic mechanisms of bipolar disorder (BD), prompting the search for unstable DNA sequences. Past studies of anticipation in BD have generally relied on observed shift in the age at onset between parental and offspring generations. Such a shift, however, may be caused by a number of other factors difficult to correct for. We investigated age at onset distributions in a sample of 161 related subjects and in a sample of “pseudofamilies” consisting of 320 unrelated subjects selected from a large epidemiological cohort using Monte‐Carlo simulation to mimic the family sample. Comparison of age at onset distributions in both samples shows a difference between the generations, but of a similar magnitude in each sample. This suggests that age at onset alone may not be a sufficient criterion of anticipation. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:804–807, 2000. © 2000 Wiley‐Liss, Inc.     

The tick-over theory revisited: Is C3 a contact-activated protein?

The tick-over theory was first introduced in the 1970s to explain the presence of the initial C3b molecules, which are able to trigger complement activation by the alternative pathway in human plasma under physiological conditions. After the identification of the thioester, the predominant hypothesis has been that this bond is hydrolyzed at a slow but constant rate by nucleophilic attack by H(2)O, leading to the generation of C3(H(2)O). Here we put forward the hypothesis that the rate of hydrolysis of C3 to C3(H(2)O) may be greatly accelerated by the interaction between C3 and a number of biological and artificial interfaces, including gas bubbles, biomaterial surfaces and different lipid surfaces and complexes. We therefore propose that C3 should preferentially be regarded as a contact activated protein rather than a target for passive, random hydrolysis in the fluid phase.     

Is adjunctive open-label zonisamide effective for bipolar disorder?

OBJECTIVE: To assess the effectiveness and safety of zonisamide in bipolar disorder. METHODS: A chart review was conducted of naturalistic treatment with zonisamide in 35 outpatients meeting DSM-IV criteria for bipolar disorder (9 males, 26 females; mean +/- SD age = 29.2 +/- 12.7; 14 with bipolar disorder type I, 6 with bipolar disorder type II, and 14 with bipolar disorder not otherwise specified). Patients received zonisamide adjunctive therapy between January 1994 and December 2004. Treatment response was defined as a Clinical Global Impressions - Improvement (CGI-I) scale score of +2 (much improved) or + 3 (very much improved). RESULTS: Zonisamide was moderately to markedly effective in 9 subjects (26%). Indication for treatment included depressive (34.3%, [12/35]), manic/hypomanic (28.6%, [10/35]), or mixed (31.4%, [11/35]) symptoms. The mean zonisamide dose was 130 mg/d for a mean duration of treatment of 27.0 +/- 32.3 weeks. Sedation (25%, [4/16]) was the most common side effect; 19/35 (54.3%) reported no side effects. 17/35 (49%) patients terminated early, mostly due to adverse effects (6/35). Using a multivariable model, predictors of response, concurrent mood stabilizers, dose and bipolar subtype (bipolar type I > type II/NOS), were controlled for in this sample. CONCLUSIONS: In 35 persons with bipolar disorder taking standard mood stabilizers and other psychotropic agents, adjunctive zonisamide appears to have modest benefit in global improvement when added to a pre-existing complex medication regimen in patients with bipolar spectrum disorder. These pilot data support the need for larger studies to test the potential efficacy of zonisamide for treatment in mood disorders.     

Is bipolar II disorder misdiagnosed as major depressive disorder in children?

OBJECTIVES: To estimate the lifetime prevalence of bipolar II disorder in children and adolescents presenting with DSM-IV major depressive disorder (MDD). METHODS: Sixty-one consecutive subjects aged < or =18 years attending the outpatient services of the Child and Adolescent Psychiatric (CAP) services of the National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India with a diagnosis of MDD were evaluated using the Missouri Assessment of Genetics Interview for children (MAGIC). Two psychiatrists, one of whom was a child psychiatrist diagnosed hypomania by consensus. RESULTS: Twelve children had a past episode of hypomania (20%), which was hitherto undiagnosed clinically. LIMITATIONS: We recruited subjects from a psychiatric hospital, thus limiting the generalizability of the finding. Sample size was relatively small and assessments were cross-sectional. CONCLUSIONS:: Our study shows that bipolar II disorder is often misdiagnosed as MDD in children. The study also highlights that the chance of diagnosing bipolarity is enhanced by using semi-structured interview in routine clinical practice.     

Is donepezil useful for improving cognitive dysfunction in bipolar disorder?

BACKGROUND: Cognitive dysfunctions are being recognized as a major roadblock to functional recovery in patients with bipolar disorders. Little is known about the treatment of these cognitive dysfunctions. Donepezil, approved to treat memory dysfunction in Alzheimer's disease, is evaluated for cognitive dysfunctions common in bipolar disorder. Of concern is some evidence that donepezil may trigger affective instability. METHODS: All bipolar disordered patients in a private practice setting treated with donepezil for memory problems were analyzed. Patients were assessed for memory improvement and change in psychiatric status with the Clinical Global Impression of Improvement Scale. RESULTS: Thirty-nine of 58 patients (67%) reported improvement with a mean score of 1.82 (standard deviation+/-0.82). Nine treatments were stopped because of side effects and 4 showed no response. No bipolar I patient received benefits. Thirty-six of 43 (84%) of bipolar II patients showed improvement. Fifty percent of bipolar NOS showed improvement. Four bipolar I patients (57%), 1 bipolar II patient (2%) and 2 bipolar NOS patients (25%) stopped donepezil due to worsening affective symptoms. LIMITATIONS: This is a naturalistic case series with a single evaluator. Other medications used in treatment were changed as clinically indicated. CONCLUSIONS: This case series suggests utility for donepezil in the treatment of cognitive problems associated with bipolar II disorder and bipolar disorder NOS. Bipolar I patients showed no improvement and a concerning trend to destabilize with donepezil treatment.     

The pattern,clinical characteristics and outcome of ESRD in Ile-Ife,Nigeria: Is there a change in trend?

Background

The prevalence of chronic renal failure and End Stage Renal Disease (ESRD) has remained high worldwide and the epidemiology has changed significantly in the last decade in industrialised countries. While there have been significant improvements in these patient''s outcomes in developed countries, their state and survival is still appalling in developing countries.

Objective

To determine the clinical pattern, presentation and management outcomes in our ESRD population over a 19-year period (1989–2007).

Methods

Seven hundred and sixty patients'' records were reviewed. Data on major causes, clinical presentation, management and survival were retrieved and collated. Data was analysed using SPSS package version 16.

Results

Their ages ranged between 15–90 years (mean ± SD; 39.9±1.67years) with male preponderance (70.3%). Major presenting complaints were body swelling and uraemic symptoms in most studied patients. The predisposing conditions included chronic glomerulonephritis, hypertension, obstructive uropathy and diabetes mellitus. Renal replacement therapy offered included HD in 556(73.2%), Continous Ambulatory Peritoneal Dialysis (CAPD) in only 9(1.2%) patients and renal transplantation in only 7(0.9%). Only 38(6.8%) survived on HD for longer than three months while 7(77.8%) CAPD patients and all transplanted patients survived for between six months and four years (p<0.00001). Median duration of survival after diagnosis for all the patients was 2 weeks (range 0–50 months).

Conclusion

End stage renal disease is still prevalent with chronic glomerulonephritis and hypertension being the common causes. Prognosis is still grave hence subsidized renal replacement therapy and preventive nephrology should be targeted in such underserved populations.     

Is sepsis a pro-resolution deficiency disorder?

Sepsis is due to a systemic inflammatory response to both infectious and non-infectious disorders; and when it leads to hypotension and organ dysfunction, septic shock occurs. Mortality in sepsis is due to multiple organ dysfunction. The early stages of sepsis are characterized by excessive generation of inflammatory mediators; however, as sepsis develops into chronic severe sepsis, immunosuppression dominates. Despite several advances in our understanding of the pathogenesis of sepsis both its prevention and management remains elusive. It is proposed that sepsis is due to failure of production of appropriate amounts of pro-resolution bioactive lipids such as lipoxins, resolvins, protectins, maresins and nitrolipids that suppress inappropriate inflammation, production of pro-inflammatory cytokines, free radical generation, and leukocyte activation and enhance resolution of inflammation and wound healing.     

Menopause and depression: Is there a link?

Aim

Depression is common and may have significant implications for the individual, their families and work and for the health care system. The menopause transition (MT) may be an ‘at risk’ time for the development of depression. This review aims to explore the relationship between depression and MT and the complex interaction between the biological, psychological and social factors that inform it.

Methods

The literature on depressive disorders and MT is reviewed.

Results and conclusions

Longitudinal studies have demonstrated an association between the menopause transition (MT) and an increase in depressive symptoms. A trend towards higher rates of depressive disorders during the MT, has also been shown, although not always reaching statistical significance. Risk factors for the development of depressive symptoms and depression in the MT include the presence of vasomotor symptoms (VMS), a personal history of depression (particularly depression that is related to pregnancy or hormonal changes through the menstrual cycle), surgical menopause, adverse life events, and negative attitudes to menopause and ageing. A treatment approach to depression during the MT exploits the biological as well as the psychosocial factors that are likely to be contributing in an individual.     

Attention deficit hyperactivity disorder with bipolar disorder in girls: further evidence for a familial subtype?

BACKGROUND: To clarify the nosologic status of girls with attention deficit hyperactivity disorder (ADHD) who also satisfy diagnostic criteria for bipolar disorder (BPD). METHODS: Using blind raters and structured psychiatric interviews, we examined 140 girls with ADHD, 122 non-ADHD comparisons and their 786 first degree relatives. Analyses tested specific hypotheses about the familial relationship between ADHD and bipolar disorder in girls. RESULTS: After stratifying our ADHD sample into those with and without BPD, we found that: (1) relatives of both ADHD subgroups were at significantly greater risk for ADHD than relatives of non-ADHD controls, (2) the two subgroups did not significantly differ in their relatives' risk for ADHD; (3) an elevated risk for bipolar disorder was observed among relatives when the proband child had BPD but not ADHD alone; (4) weak evidence of cosegregation between ADHD and BPD, and (5) no evidence of a trend for random mating between ADHD parents and those with mania. LIMITATIONS: Limitations of this study include the lack of direct interviewing of probands and the limited number of ADHD/BPD probands available. CONCLUSIONS: These findings extend to girls what was previously documented in boys and suggest that comorbid ADHD with BPD in girls is familially distinct from other forms of ADHD and may be related to what others have termed childhood onset BPD. Future work could determine if this subgroup has a characteristic course, outcome and response to treatment.     

The pathogenesis of febrile seizures: Is there a role for specific infections?

Although fever is regarded as the main trigger in the pathogenesis of febrile seizures (FS), it is not supposed to be the unique causative factor. In FS, there is a strong familial predisposition. This does not exclude infections as a causative factor because subtle genetic polymorphisms have been demonstrated to affect the course of infections. We review the literature on: (1) the role of fever, especially the height of temperature, its cause, and metabolic effects induced by temperature; (2) the role of heredity; (3) the role of cytokines which play a role in the induction of fever; and (4) the role of type of infection, with emphasis on newly identified agents and improved diagnostic techniques. With modern molecular techniques such as PCR, viruses have been detected in the CSF far more often than previously thought, even in the absence of pleocytosis of the CSF. This makes it difficult to distinguish FS from acute encephalitis. FS may be caused by neuroinvasion or intracerebral activation of viruses. Further studies should focus on these options because therapeutic intervention is possible and may prevent late sequelae such as recurrent FS and subsequent epilepsy.