Recent development in molecular genetics, in particular linkage studies, offered possibilities of identification of the gene associated with the ethiopathology of bipolarity. This possibility has not materialized. However, in spite of the previous statement there is reliable information stating that there are genetic links basis for this disorder. This evidence originates in family studies, adoption studies and findings in mono and dizygotic twins. Family members in first degree of relationship with bipolar patients have an 8% probability of developing Bipolar Affective Disorders and concordance of monozygotes versus dizygotes is 61% vs a 23% respectively. There is, however, lack of a mathematical inheritance model that explains the distribution of Bipolar Affective Disorders in the numerous families studied. However, linkage studies have not been able to demonstrate chromosomic locations that can be associated in a reproducible way with Bipolar Affective Disorders. The following are chromosomic locations with contradictory linkage types: Xq28, 11p15, 18p, 18q, Xq27, 5q35, 21q22, 12q23, 16p13 and 4p16. [22, 33, 5, 1, 7, 31].

Neurochemical and neuroendocrine factors of bipolar affective disorders.

All research reports in bipolar disorders suggest that the physiopathology of this disease could be extraordinarily complex and dependent on multiple interactions of neurochemical and/or neuroendocrinological nature. The great symptomatic variability of pathology has rendered the etiopathogenic study difficult. More than 90% of biological signs that have been replicated correspond to status markers (signs that are detectable only during symptomatic episodes).

A more detailed description of research findings and etiopathogenical hypothesis in bipolar disorder are beyond the objectives of this paper. However, we will mention only the biological systems that are more frequently involved.  (Table I) [1, 37].

Table I. 
Neurochemical and endocrine changes associated to the
physiopathology of Bipolar Affective Disorders

Involvement of neurological circuitry

There is little direct evidence in relation to the neurofunctional impairment that is responsible for the pathogenic changes of ABD. However, there is a series of theoretical models designed on the basis of clinical and experimental findings that allow the hypothesis that there are neurocircuitry probably involved in this disorder. The most current model related to the neuro-biology of affectivity was defined by Cummings in 1993 and consists of a series of cortical and subcortical structures with highlighted participation of the prefrontal cortex, striatum and thalamus (figure 1) [12]. Detailed descriptive studies have demonstrated psychopathological changes that are induced by selective lesions of the different components of the general affectivity circuitry (Table II). In these structures most probably we will find the functional substratum of bipolarity and F. Varela, neurobiologist, has defined the most probable mechanism of affective phenomena. His hypothesis is widely known as the “neuronal synchronicity and large-scale integration” [36]. The central concept of his theory describes the functioning of mental phenomena as non-directional processes that have been described as “emergent properties”. At any time affective phenomena would emerge starting with a simultaneous action of different neuronal circuits synchronized in a scale of milliseconds. And according to this theoretical model only the synchronic action of a series of neuro-anatomical-functional structures would determine the appearance of an affective moment. Therefore, an impairment or damage to one segment of an affective synchronic segment would determine a clinical picture with similar psychopathological characteristics.

Table II
Clinical correlation of neuro- anatomical selective impairment

NeuroSPECT findings in bipolar disorder

Research studies that address homogeneous bipolar disorders population, report on similar findings. These papers report on at least two coincidental concepts: 1) Abnormalities of Tc99m HMPAO uptake in frontal cortex, subgenual region, anterior cingulate gyrus and superior temporal gyrus and 2) NeuroSpect findings appear to be dependant on the dominant clinical features during the acquisition of NeuroSPECT and appear to be, therefore, markers of the Clinical State. The phases that have been evaluated correspond to depression or mania, without information on periods of eutimic mood. In table III we describe some of the findings reported and the imaging techniques that were used [28, 15, 32, 20, 9, 35].

Table III.
NeuroSPECT functional findings in BD